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CustomCornea® LASIK Physician's Booklet - Mixed Astigmatism

Alcon

Excimer Laser System

PROFESSIONAL USE INFORMATION MANUALFOR CustomCornea® LASER ASSISTED IN-SITU KERATOMILEUSIS

(LASIK)PHYSICIAN'S BOOKLET

For Mixed Astigmatism of 1.OOD) to less than 5.000) cycloplegic cylinder magnitude

RESTRICTED DEVICE: U.S. Federal Law restricts this device to sale, distribution, anduse by or on the order of a physician or other licensed eye care practitioner. U.S. FederalLaw restricts the use of this device to practitioners who have been trained in itscalibration and operation, and who have experience in the surgical management andtreatment of refractive errors.

This document provides information concerning the intended clinical use of theLADARVision®4000 Excimer Laser System. For complete information concerningsystem components, safety instructions, installation, maintenance, and troubleshootingrefer to the LADARVision®4000 Excimer Laser System Operation Manual.

Carefully read all instructions prior to use. Observe all contraindications, warnings, andprecautions noted in these instructions. Failure to do so may result in patient and/or usercomplications.

Alcon, Inc.2501 Discoveiy Drive, Suite 500

Orlando, FL 32826

Tel: (877) 523-2784Fax: (407) 384-1677

Outside the U.S., contact your local Alcon representative

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C 2006 Alcon, Inc.

All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means,electronic or mechanical, including photocopying, recording, or any information storage and retrieval system,without permission in writing from Alcon, Inc.

REVISION CONTROL SHEET

Revision Description Date

A DCN 10065 -original release

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TABLE OF CONTENTS

1. GENERAL SAFETY CONSIDERATIONS ............................................................................... 52. DEVICE DESCRIPTION ......................................................................................................... 5

A. WAVEFRONT MEASUREMENT DEVICE (WMD) ......................................................... 5B. M ICROKERATOME ................................................................................................. 6C. CUSTOMCORNEA® SURGERY PLANNING SOFTWARE ............................................... 7D. LADARViSION®4000 EXCIMER LASER SYSTEM ..................................................... 7

3. INDICATIONS, CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, ADVERSEEVENTS AND COMPLICATIONS ........................................................................................ 12A. INDICATIONS FOR USE ........................................................................................ 12B. CONTRAINDICATIONS .......................................................................................... 12C. W ARNINGS ......................................................................................................... 12D. PRECAUTIONS .................................................................................................... 13E. ADVERSE EVENTS AND COMPLICATIONS ............................................................... 14

4. CLINICAL STUDY ................................................................................................................. 15A. INTRODUCTION .................................................................................................. 15

B . R E S U LT S .......................................................................................................... 171. Dem ographics ............................................................................................ 172. Accountability ............................................................................................ 173. Preoperative Cycloplegic Refraction Param eters ...................................... 184. Key Effectiveness Outcom es .................................................................... 195. Stability of M anifest Refraction ................................................................. 296. W avefront Outcom es .................................................................................317. Key Safety Outcomes ................................................................................ 348. Change in Contrast Sensitivity .................................................................. 389. Patient Questionnaire ................................................................................ 3910. Retreatm ent ............................................................................................... 4011. Statistical Analysis Outcom es .................................................................... 4112. Com parative Analysis by Defocus Type .................................................... 43

C. TRACKING EFFECTIVENESS ................................................................................. 465. PLANNING AND PROCEDURES ......................................................................................... 47

A. PATIENT SELECTION .......................................................................................... 47

B. OPERATIVE PROCEDURE ............................................................................. ...... 48

1. Centration and Registration ....................................................................... 492 . P u p il D ila tio n ... ........................................................................................... 4 93. Laser Calibration ....................................................................................... 504 . A b la tio n ............................................. 5...........................1....................... .5 1

C. POSTOPERATIVE PROCEDURE ................... 5............... .................. ............... 52

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1. GENERAL SAFETY CONSIDERATIONS

"WARNING:" - Identifies conditions or practices that could result in damage to equipment orother property, personal injury, or loss of life.

WARNING: Specific training from Alcon or an authorized representative of Alcon is requiredbefore anyone is qualified to operate the LADARVision®4000 Excimer Laser System. Read andunderstand this manual and the LADARVision®4000 Excimer Laser System Operation Manualprior to operating the system.

Refer to the LADARVision®4000 Excimer Laser System Operation Manual for additionalwarnings regarding use of the LADARVision®4000 Excimer Laser System.

2. DEVICE DESCRIPTION

A. WA VEFRONT MEASUREMENT DEVICE (WMD)

The first step in performing CustomCornea® LASIK surgery is to perform a wavefrontexamination on the patient using a wavefront measurement device (WMD) compatible with theLADARVision®4000 Excimer Laser System. At the present time, the only compatible WMD isthe Alcon LADARWave® CustomCornea® Wavefront System.

The LADARWave® CustomCornea® Wavefront System is indicated for measuring, recording.and analyzing visual aberrations (such as myopia, hyperopia, astigmatism, coma and sphericalaberration) and for displaying refractive error maps of the eye to assist in prescribing refractivecorrections. This device is enabled to export wavefront data and associated anatomicalregistration information to a compatible treatment laser with an indication for wavefront-guidedrefractive surgery.

Essential features of the compatible WMD are as follows:

Patient Fixation and Fogging

The WMD includes a fixation optical subsystem that provides the patient with an unambiguousfixation point. In addition, the fixation subsystem includes adjustable optics to compensate forthe patient's inherent refractive error. The optics are used to "fog" the eye, first clarifying thefixation target and then it optically adjusts beyond the patient's far point to minimizeaccommodation.

Centration

Prior to dilation, the WMD is used to record the geometric relationship between the naturaidaytime pupil center and the limbus of the eye. This information is then used to center thewavefront measurement and subsequent ablative treatment on the natural line of sight.

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Wavefront Measurement

The WMD measures the wavefront profile of the eye with a high degree of accuracy andcharacterizes the profile using Zernike polynomials. The pupil must be large enough so thatvalid wavefront data can be obtained over a large area. Higher-order aberrations are moresignificant at night when the pupil is naturally larger. Therefore, when treating these aberrations,measurement over a large pupil provides the greatest utility.

Registration

The WMD uses synchronized video imagery and on-screen software reticules to record therelationship of the wavefront data to the limbus of the eye and to ink marks applied to the sclerajust before the wavefront exam. This registration information is used to position the excimerablation profile at the correct comneal location and cyclotorsional angle.

Data Export

The WVMD has the ability to export the wavefront examination data as an electronic file toremovable media for transfer to the LADARVision®4000 System. The electronic file isstructured in a specific format and contains essential patient information, centration/registrationinformation, and the detailed aberration data. In addition, the electronic file is encrypted in amanner that can only be deciphered by the LADARVision®~4000 System.

B. MICROKERA TOME

A microkeratome is used to achieve a partial thickness cut of the cornea, which creates a "flap"as part of the LASIK procedure. The microkeratome is a precision instrument used in performinglamellar corneal resections. This instrument cuts a precise corneal disc of pre-selected thicknessand diameter. The system generally consists of a head, plates, ring, handle, wrenches, shaft,motor, hand-piece, disposable blades, and power supply with footswitches and power cords. Thesystem is completed with the applanation lens set, tonometer, corneal storage jar, optical zonemarker, spatula, stop attachment, and digital thickness gauge.

Microkleratomes Used in the Clinical Trial.

The microkeratomes used in the clinical trial included the BD K-40001 (manufactured byBecton-Dickinson), Hansatome 2 (manufactured by Bausch & Lomb), and the Moia 3 CB andLSK (manufactured by Moria).

BD K-40O00 TM of Becton, Dickinson and Company- lansalonie Reg. TM of Bausch & Lomb IncorporatedAMot ia Reg. TM of Moria SA

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C. CUSTOMCORNEA8 SURGERY PLANNING SOFTWARE

The CustomCornea® Surgery Planning Software is a stand-alone computer application linkingthe diagnostic wavefront data from the WMD with the surgical treatment on theLADARVision®4000 Excimer Laser System. The planning software allows refinement ofsurgical parameters within the approved wavefront-guided indication for theLADARVision®4000 System, calculates ablation depth, checks for treatment eligibility, andexports all messages and warnings to the excimer laser system.

After completing the surgery planning tasks, the planned treatment file is transferred to theLADARVision®4000 System. The LADARVision®4000 System software imports the treatmentfile, calculates the excimer treatment pattern, and performs the surgery.

D. LADARVISION'4000 EXCIMER LASER SYSTEM

The LADARVision®4000 System excimer laser beam is of Gaussian profile and small indiameter (<0.90mm). Comeal sculpting is achieved by delivering hundreds to thousands ofexcimer laser pulses to the eye in a complex pattern of spatially overlapping spots, and precisionof this process depends on accurate placement of the laser pulses. The LADARVision®4000Excimer Laser System incorporates the LADARTracker® closed-loop eye-tracking system totrack and compensate for patient eye motion, including saccadic movements, during proceduresso that each excimer laser pulse is delivered to the appropriate location on the cornea.a) Excimer Laser CharacteristicsThe ultraviolet laser used in the LADARVision®4000 Excimer Laser System is an argon fluorideexcimer laser. This laser produces 10 nanosecond pulses of ultraviolet radiation at a wavelengthof 193 nanometers. The laser repetition rate is approximately 60 pulses per second.Characteristics of the laser beam at the corneal treatment plane are shown below:Treatment Plane Characteristics of the LADARVision®4000 System Excimer Laser Beam

Pulse energy (mJ) 2.4 - 3.0Beam diameter (mm) a < 0.90Average fluence (mJ/cm 2) b 180-240

Note (a): The Gaussian beam diameter is defined as the mean of the semi-major and semi-minor axes of theelliptical beam cross-section and is the I/e width in the Gaussian fluence distribution.

Note (b): This is the calculated average value per pulse of the laser fluence over the ablated area.

Additional features of the LADARVision®4000 Excimer Laser System include:

Optical Transmission System

The excimer laser passes through an optical telescope, followed by reflection off a series ofmirrors which position the excimer laser pulses in the correct locations at the treatment plane.Tracking mirrors also compensate for patient eye motion, as detected by the LADARTracker ®

system.

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Energy Monitoring/Control

An energy monitor is mounted at the output of the LADARVision®4000 System. Prior totreatment, this energy monitor ensures that the laser pulse energy delivered to the eye will bebetween 2.4 and 3.0 mJ. During treatment, the detector monitors laser operation.

Gas Handling

The excimer laser enclosure holds the laser, gas bottle, and gas-plumbing manifold. The gasbottle contains the pre-mixed excimer laser gas, which contains neon as the buffer gas, inaddition to argon and fluorine. The initial pressure in the gas bottle is 2000 PSI. The outletnozzle of the gas bottle contains a flow restrictor valve. Gas from the bottle flows to a fluorine-compatible gas regulator, which reduces the line pressure to 55 PSI. Two gas lines exit theregulator. One leads directly to the outlet line of the laser enclosure. In the event of a diaphragmfailure, excimer gas will flow from the regulator down this line and out of the enclosure. Outsidethe laser enclosure, the gas flows through a charcoal-based filter (to remove the F2) beforeventing into the room. The second gas line exiting the regulator leads to the excimer lasercavity. At the line connection to the cavity there is a solenoid valve, which responds tocommands from the laser control electronics board. A second solenoid valve exists at the gasoutlet port of the laser cavity. The outlet gas line also leads out of the laser enclosure andthrough the charcoal filter.

Eye Tracking System

The LADARVision®4000 System utilizes the LADARTracker® active closed-loop eye trackingsystem to track and compensate for eye motion during refractive laser surgery. The word"active" here is used to denote two important characteristics of the device. First, theLADARTracker® system actively tracks the position of the eye by irradiating it with pulses of905 nm infrared "eye-safe" energy and analyzing characteristics of the returning laser radiation.This measurement occurs 4000 times each second in order to detect even rapid eye motionbefore significant movement of the cornea has occurred.

The LADARTracker® system is also "active" in the sense that it actively compensates for thedetected motion, rather than simply disabling the treatment laser when the eye position exceedssome tolerated error range. The LADARTracker ® system includes two mirrors that arecontinually repositioned to keep the eye centered in the field of view of the treatment laser. Anindependent set of mirrors is used to translate the treatment beam around within this field ofview, delivering the ablation pulses to the cornea in a predetermined spatial pattern. Thecombined system allows for each ablation pulse in the complex pattern to be delivered to theappropriate corneal site, even in the presence of substantial eye movement.

The LADARTracker® system is designed so that precise mirror movements during the course ofeach surgery are recorded. Because the geometry involved is known, exact eye movements canbe calculated from the compensatory movements of the mirrors. It is not possible to performsurgery using the LADARVision®4000 System without the LADARTracker® system engaged.and no patient has ever been treated without concurrent tracking.

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CustomCornea~' LASIK Physician's Booklet - Mixed Astigmatism

Operating Microscope

The stereo viewing operating microscope is located in the optics head. The dual optical paths areindependent of the excimer beam path and the LADARTracker®~ system mirrors. Oblique, omni-directional microscope lighting on either side of the system output window provides visibleillumination of the treatment plane. The operating microscope optical system is completelyindependent from the eye tracking optical system and does not provide "tracked" imagery of thepatient eye.

Fixation Target

A visible fixation target is mounted in the system to facilitate the patient looking in the directionof the treatment excimer beam. The fixation target consists of a light emitting diode (LED), apinhole aperture, an edge-illuminated reticule, and a lens. The lens, in combination with a300mm focal length achromat in the operating microscope optical path, places the LED atinfinity focus from the patient's perspective. The edge-illuminated reticule is a clear, flat etchedglass with two sets of horizontal lines. For proper eye alignment, the patient is instructed to shiftposition until the LED pinhole light is centered within the parallel lines on the reticule and thento maintain that fixation during treatment.

Moveable Bed

A motorized patient bed, which moves on X, Y and Z axes, smoothly and rapidly positions thepatient and facilitates bilateral procedures. The bed controls are located on the Control Consoleand the Control Module. The longitudinal motion range is approximately 15", so that the patientcan lie on the bed and then be moved into position under the laser head. The lateral range ofmotion is 4", allowing surgery to be performed on either eye. The vertical range of motion is 3",allowing adjustment for the proper distance from the laser aperture to the eye for varying headsizes. Each axis has a continually variable speed control for coarse and fine positioning.

Cross Beam Patient Positioning

Cross beam Class I lasers are used to place the cornea at a predetermined height for properablation. The cross beam laser sub-system consists of two laser line generators attached to theleft and right sides of the upper optical module. The laser diode sources produce 0.9 mwattseach at 633nm. The beam of each red-wavelength laser is transmitted through an absorptiveneutral density filter, which attenuates the laser by 97%, and a polarizer. The output of eachpolarizer is reflected off a stationary fold mirror. The two mirrors are aligned such that the twobeams are vertically aligned (one above the other) on the left sciera/linmbus boundary when theapex of the cornea is 8 inches below. the laser output window. This provides the operator/surgeonwith an easy method of setting the height of the patient's eye during centration and surgery.

The maximum laser power at the eye is less than 15 llwatts for each laser. The lasers areseparated by 103nmm and are 209nmm from the eye. With this geometry, the laser spots areseparated on the retina by several times their diameter so the energy is not additive. Given thewavelength and power, the maximum permissible Class I exposure duration is 4 minutes and30 seconds. When the cross beam lasers are turned on, a 2-mninute automatic time out isactivated to ensure the safe exposure limit is not exceeded. The cross beam lasers comply withClass I accessible emission limits for laser radiation in 21CFRIO40 as wvell as ANSI Z136.1-1993.

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CustomCorneao LASIK Physician's Booklet - Mixed Astigmatism

Plume Removal System

The plume removal system is housed within the calibration stage. During surgery, the plumeremoval system is deployed to a pre-determined height and provides a constant level of plumeremoval during ablation. The plume is evacuated to a filter cartridge that is contained within thesystem. This filter cartridge is inspected and replaced during preventative maintenanceperformed by Alcon Technical Service personnel.

System Software

The LADARVision®4000 System software controlling the proprietary excimer laser runs on anIntel Pentium4-based personal computer under a Microsoft Windows 5 operating system. Thesoftware enables the user to:

* properly center the treatment;

* make adjustments in the X and Y axes;

* adjust for cyclotorsion and correctly reference astigmatism; and

* place a hinge guard to protect the flap during surgery.

In addition, the software enables the user to properly match the alignment of the wavefront mapto the ablation.

Laser Shot Patterns

The LADARVision®4000 System software calculates the "laser shot pattern," i.e., the number ofexcimer laser pulses to deliver to the eye and the required position of each pulse on the cornea,based on the desired refractive correction and the current laser calibration. The system softwarealso calculates a sequence to fire the pulses in the shot pattern such that no corneal site isrevisited by the excimer beam for a finite interval. The laser firing sequence is designed toprovide a gradual corneal curvature from the starting surface shape to the corrected final profile.

Rather than the refractive correction being entered manually by the physician based on phoropterrefraction, the CustomCornea® treatment requires that the pre-operative aberrations in the eye bemeasured with a wavefront measurement device. The treatment is based on Zernike data derivedfrom a wavefront measurement device, including treatment of lower-order sphere andastigmatism components and higher-order components, such as coma and spherical aberration.

4 Intel and Pen/ium Reg. TM of Intel CorporationMAicrosoft and Windows Reg. TM of Microsoft Corporation

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The electronic file that the LADARVision®4000 System receives from the wavefrontmeasurement device includes the following information:

* Patient information, including name, identification number, and clinical prescription.* Eye information, including OD/OS and the geometric relationship of the wavefront data to

the limbus and to the pupil center.* Wavefront information, including a Zemike polynomial representation of the wavefront and

the physical radius of that description.

The excimer laser beam characteristics (i.e., pulse energy, firing rate; fluence distribution at thetreatment plane) are the same for Conventional and CustomCornea® treatment modalities. TheConventional LADARVision®4000 System treatment utilizes sphere, cylinder and axiscomponents entered manually by the operator to generate the ablation profile. TheCustomCornea ® LASIK shaping algorithm utilizes aberration information unique to a given eyethat is obtained from the WMD to guide the ablation of the cornea. The wavefront information isregistered to the anatomical geometry of the eye using the WMD while the patient is sittingupright. This registered alignment information is passed to the LADARVision®4000 System,which both permits for the compensation of this alignment information due to the naturalcyclotorsion incurred when the patient assumes a prone position and uses the geometryinformation to accurately position the customized ablation profile on the eye.

CustonCorneao Ablation Zones

For CustomCornea® ablations, the standard optical zone is 6.5mm with a blend zone of 1.25mmfor a total ablation zone of 9.0mm.

Safety

The LADARVision®4000 System contains a Class IV laser that conforms to the US FDA 21CFR 1040 Radiological Health requirements. The laser system was designed to meet thefollowing safety requirements:

* UL 260 1-1 (previously UL 544)* CSA22.2No. 601.1-M90

* IEC 60825-1* EN60601-1-1-2 and EN60601-2-22

NOTE: Additional details regarding operation of this laser can be found in theLADARVision®4000 Excimer Laser System Operation Manual.

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CustomCornea ®LASIK Physician's Booklet - Mixed Astigmatism

3. INDICATIONS, CONTRAINDICATIONS, WARNINGS,PRECAUTIONS, ADVERSE EVENTS AND COMPLICATIONS

A. INDICATIONS FOR USE

The LADARVision®4000 Excimer Laser System is indicated for wavefront-guided LaserAssisted In-Situ Keratomileusis (LASIK):

* for the reduction or elimination of mixed astigmatism of 1.00D to less than 5.00Dcycloplegic cylinder magnitude at the spectacle plane, which is greater than the spheremagnitude, and the cylinder and sphere have opposite signs;

* in patients who are 21 years of age or older; and

* in patients with documented stability of refraction for the prior 12 months, asdemonstrated by a change in sphere and cylinder of less than or equal to 0.50D.

B. CONTRAINDICATIONS

Wavefront-guided LASIK is contraindicated in:

* pregnant or nursing women.

* patients with autoimmune, collagen vascular, or immunodeficiency diseases.

* patients with signs of keratoconus.• patients who are taking one or both of the following medications: isotretinoin (Accutane 6)

or amiodarone hydrochloride (Cordarone).

C. WARNINGS

Wavefront-guided LASIK is not recommended in patients who have:

* diabetes.

* a history of herpes simplex or herpes zoster keratitis.

* significant dry eye that is unresponsive to treatment.

* severe allergies.

A minimum pre-operative pupillary dilation of 7amm and a maximum dilation of 1 hnm must beachieved and maintained in all patients throughout the refractive procedure to optimize trackingperformance.

6,Accutane Reg. TM of Hoffniann-La Roche Inc.7Cordarone Reg. TM of Sanofi-Aventis

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D. PRECAUTIONS

The safety and effectiveness of the LADARVision®4000 System for wavefront-guided LASIKcorrection of mixed astigmatism have NOT been established in patients:

* with unstable mixed astigmatism.

* with ocular disease, comeal abnormality, previous comeal or intraocular surgery, ortrauma in the ablation zone.

* with a residual posterior stromal corneal thickness less than 250 microns at thecompletion of ablation.

* with a history of glaucoma.

* who are taking the medication sumatripin succinate (Imitrex).

* under 21 years of age.

* over the long term (more than 9 months after surgery).

* for treatments of mixed astigmatism of less than 1.00D cycloplegic cylinder magnitude orfor 5.0OD or greater cycloplegic cylinder magnitude.

* for retreatment with wavefront-guided LASIK.

The safety and effectiveness of wavefront-guided CustomCornea® LASIK have only beenestablished for an optical zone of 6.5mm and an ablation zone of 9.0mm.

Pupil size should be evaluated under mesopic illumination conditions. Patients with largemesopic pupils Ž> 6.5mm (optical zone size) should be advised of the potential for negativeeffects on vision after surgery, such as glare, halos, and nighttime driving difficulty.

Preoperative evaluation for dry eye should be performed. Patients should be advised of thepotential for dry eyes post-LASIK surgery.

The physician's adjustment of defocus has not been studied, and its effects on the safety andeffectiveness outcomes of this procedure are unknown.

Please be advised that eyes with prior intraocular or corneal surgery of any kind were excludedfrom clinical trials with the LADARVision®4000 System. Safety and effectiveness, as well astracking performance, have not been established for such eyes. Although the tracking systemmay acquire track in surgically altered eyes prior to ablation, the optics of the eye may change inthe context of the ablation to potentially interfere with further tracking and compromise thecompletion of the ablation. Medical judgment should be exercised in the use of theLADARVision®4000 System in pseudophakic patients and others who have had prior intraocularor corneal surgery.

8 lnitrex Reg. TM of Glaxo Group Limited

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E. ADVERSE EVENTS AND COMPLICATIONS

Cumulative adverse events and complications reported at any postoperative visit up to 9 monthsin the clinical study for CustomCornea® LASIK correction of mixed astigmatism aresummarized in Table 1. The data meet the safety criteria established in the FDA GuidanceDocument of less than 1% occurrence of each type of adverse event and less than 5% overall.

Table 1. Summary of Adverse Events and ComplicationsAt Any Postoperative Visit

ADVERSE EVENTS n/N %

Miscreated flap (related to microkeratome) 2/1 1 It 1.8%

Corneal infiltrate (related to viral epidemic keratoconjunctivitis) 1/110 0.9%

COMPLICATIONS

Grade _> I Superficial Punctate Keratitis (SPK) at one month or later 11/110 10.0%

Epithelium in the interface 6/11't 5.4%

Diffuse lamellar keratitis (DLK) 5/110 4.5%

Pain at one month or later 2/110 1.8%

Foreign body sensation at one month or later 1/110 0.9%

t One eye did not receive laser ablation after the miscreated flap and was not included inthe analysis of eyes receiving laser treatment (N=1 11).

There were no reports of the following adverse events and complications in the clinical study:

* corneal edema at one week or later;

* corneal epithelial defect (central or peripheral) at one month or later;

* decrease in best spectacle corrected visual acuity (BSCVA) of more than 10 letters(> 2 lines) not due to irregular astigmatism, as shown by hard contact lens refraction atsix months or later;

* epithelium in the interface with a loss of BSCVA of 2 or more lines;* intraocular pressure increase of more than 10 mmHg above baseline;* intraocular pressure of more than 25 mmHg;

* late onset ofcorneal haze at six months or later with a loss of BSCVA of 2 or more lines;* melting of the flap;

* misaligned flap;

* retinal detachment; and* retinal vascular accident.

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4. CLINICAL STUDY

A. INTRODUCTION

The study in the U.S. using the LADARVision®4000 System began as a prospective,randomized, unmasked, and multi-center trial, where one eye of the patient receivedCustomCornea ® LASIK correction using data from a wavefront system and the fellow eyereceived a Conventional treatment based on phoropter cycloplegic refraction. For this initialsubgroup of patients, the fellow eye served as a contralateral control.

Upon providing data to support expansion of the number of patients for enrollment, the U.S.study design was changed to a prospective, non-randomized, unmasked, and multi-center trialwhere one or both eyes of a patient received wavefront-guided CustomCornea® treatment. Theprimary control was the preoperative state of the treated eye for comparison to postoperativeoutcomes. An equivalent study design was also in progress under a Canadian protocol. Datafrom the U.S. and Canadian studies were pooled since both protocols were equivalent in terms ofthe inclusion and exclusion criteria, study procedures, patient measurements, and the treatmentapplied to the eye.

The objective of the multi-center clinical investigation was to establish safety and effectivenessof wavefront-guided CustomCornea® LASIK correction of mixed astigmatism. Patients werefollowed at I day, I week, and 1, 3, 6, and 9 months postoperatively. All eyes were required tobe treated for a target of emmetropia. All surgeries performed in the study were subject toapproval by the Sponsor.

Recruited patients had the study details and follow-up requirements explained to them and wereasked to sign an Informed Consent Document preoperatively. To be eligible for the study, mixedastigmatic patients must have had a preoperative cycloplegic refraction at the spectacle plane of> O.OOD to +6.OOD sphere with < O.OOD to -6.OOD astigmatism (minus cylinder convention) withan absolute cylinder magnitude greater than the sphere magnitude. Enrollment of mixedastigmatic eyes in the study occurred over the preoperative cycloplegic refractive range of+0.25D to +4.25D sphere with -1.00D to -6.00D astigmatism and -1.38D to +1.63D sphericalequivalent (SE).

Stability of refraction must have been established and documented using previous clinicalrecords or measurement of spectacles. Stability was demonstrated by a change in the manifestsphere and cylinder over the prior 12 months of less than or equal to 0.50D. If a year-oldrefraction was not available, the change in refraction must have been 0.50D or less per year sincethe last documented refraction in both the manifest sphere and cylinder to a 1.00D maximum SEchange.

The manifest and cycloplegic refraction measured at the preoperative examination must havebeen within 1.00D of each other in the sphere and cylinder components. In addition, thecycloplegic refraction could not differ by more than 1.00D in sphere or cylinder from theattempted correction determined by the wavefront system.

For the contralateral treatment group, the cycloplegic refraction between the patient's two eyescould not differ by more than 1.00D in sphere or cylinder. In addition, patients must have beenwilling to have LASIK correction in both eyes within a 2-week period. These two criteria werenot applicable to patients treated under the bilateral CustomCornea® treatment study design.

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Patients must have been at least 18 years of age and had a BSCVA of 20/25 or better in theoperative eye(s). Patients must have been willing to return for scheduled follow-up examinationsfor 9 months after surgery and have their eyes pharmacologically dilated at the required visits.

Patients who were contact lens wearers were requested to discontinue contact lens wear for aminimum of 2 weeks for soft contact lenses and 3 weeks for hard contact lenses (RGP/PMMA)prior to the preoperative examination. Patients who had previously worn hard lenses wererequired to have two examinations conducted 2 to 3 weeks apart to show stability of refractionwithout lens wear. Prior to surgery, patients were not to wear their contact lenses in theoperative eye(s) for 2 to 3 weeks for soft and hard contact lenses, respectively.

Patients who exhibited any of the following conditions were excluded from the study:

* previous corneal, intraocular, or strabismus surgery in the operative eye(s)* history of active clinically significant or vision threatening ocular disease or pathology* clinically significant corneal scar within the ablation zone or corneal abnormality such as

recurrent erosion or severe basement membrane disease* signs of keratoconus* irregular corneal astigmatism* history of herpes keratitis* autoimmune or connective tissue disease, clinically significant atopic syndrome, or

diabetes- use of chronic systemic corticosteroids or other immunosuppressive therapy* use of systemic medication with significant ocular side effects* pregnant or nursing• use of ophthalmic medications other than artificial tears for treatment of an ocular

pathology* severe dry eye syndrome unresolved by treatment* known allergy to study medications* glaucoma or glaucoma filtering surgery* participation in another ophthalmic clinical trial* calculated residual posterior stromal thickness of less than 250 microns* inability to achieve a pupillary dilation ofŽ> 7mm* at risk of angle closure• an inability to obtain a clear and complete wavefront image

The primary effectiveness parameters for this study were: improvement of uncorrected visualacuity (UCVA); predictability and stability of manifest refraction spherical equivalent (MRSE)and manifest cylinder; reduction of wavefront error, including higher-order aberrations; andpatient satisfaction. The safety parameters for this study were: preservation of BSCVA; absenceof significant findings in slit lamp and fundus examination; absence of significant intraocularpressure (lOP) elevation: and incidence of complications and adverse events.

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B. RESULTS

1. Demographics

A total of 110 eyes of 63 patients were enrolled in the Primary Cohort. The demographics of thestudy population (Table 2) were typical for a refractive surgery trial performed in the U.S. Themean + standard deviation patient age was 40.6 ± 10.7 years with a range from 20 to 60 years.The majority of patients were Caucasian (94.5%) and the remaining patients were Hispanic(3.6%) and Indian (1.8%). Slightly more females (53.6%) than males (46.4%) participated in thestudy. The distribution of right and left eyes that received treatment was approximately equal(49.1% vs. 50.9%). While most patients (64.5%) did not wear contact lenses prior to surgery,32.7% wore soft contact lenses and 2.7% wore rigid gas permeable (RGP) lenses.

Table 2. Demographics

110 Eyes of 63 Enrolled PatientsAge (In Years)

Average ± Standard Deviation 40.6 ± 10.7Minimum to Maximum 20 to 60

Race N % EyesCaucasian 104 94.5%

Hispanic 4 3.6%Indian 2 1.8%

Gender Female 59 53.6%Male 51 46.4%

Eye Left 56 50.9%Right 54 49.1%

Contact Lens History None 71 64.5%Soft 36 32.7%

Rigid Gas Permeable (RGP) 3 2.7%

2. Accountability

The accountability for this study was > 98.2% at all postoperative intervals (Table 3).Postoperative data were available for 110 eyes (100%) up to 6 months and for 108 eyes (98.2%)at 9 months. One patient (2 eyes) missed the 9-month visit because the patient moved out of thecountry prior to the opening of the 9-month visit window.

Table 3. Accountability at Each Visit

I MONTH 3 MONTHS 6 MONTHS 9 MONTHSTotal Eyes Enrolled n 110 110 110 110Available for Analysis n 110 110 110 108

% 100.0% 100.0% 100.0% 98.2%Unavailable Missed Visit 000

% 0.0% 0.0% 0.0% 1.8%% Accountability =[available/(available + unavailable)] / 100.00 100.0% 100.0%

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3. Preoperative Cycloplegic Refraction Parameters

The study population of mixed astigmatic eyes had a preoperative cycloplegic cylindermagnitude greater than the sphere in minus cylinder convention. Preoperative cycloplegicrefractive range was +0.25D to +4.25D sphere with -1.00D to -6.00D cylinder and -1.38D to+1.63D spherical equivalent. The mean ± standard deviation for the preoperative cycloplegicrefraction was +1.50D ± 0.94D sphere, -2.90D ± 1.20D cylinder and +0.06D + 0.65D sphericalequivalent. Table 4 displays the number of eyes stratified by preoperative cycloplegic sphereand cylinder. Table 5 displays the number of eyes stratified by preoperative cycloplegicspherical equivalent and cylinder.

Table 4. Preoperative Cycloplegic Refraction Stratified by Sphere and Cylinder

CYLINDER MAGNITUDE (D) IN MINUS CYLINDER CONVENTION

SPIIERE (D) -1.00 to -2.00 to -3.00 to -4.00 to -5.00 to TOTAL-1.99 -2.99 -3.99 -4.99 -6.00

> 0.O0 to +0.99 n/N 15/110 14/110 7/110 0/110 0/110 36/110% 13.6% 12.7% 6.4% 0.0% 0.0% 32.7%

-4-1.0 to±1L99 n/N 9/110 19/110 10/110 3/110 0/110 41/110% 8.2% 17.3% 9.1% 2.7% 0.0% 37.3%

n/N 0/110 4/110 6/110 9/110 4/110 23/110+2.00 to +2.99% 0.0% 3.6% 5.5% 8.2% 3.6% 20.9%

+3.00 to +3.99 n/N 0/110 0/110 2/110 5/110 2/110 9/110% 0.0% 0.0% 1.8% 4.5% 1.8% 8.2%

+4.O0to +5.00 ln/N 0/110 0/110 0/110 0/110 1/110 1/110% 0.0% 0.0% 0.0% 0.0% 0.9% 0.9%

TOTAL n/N 24/110 37/110 25/110 17/110 7/110 110/110% 21.8% 33.6% 22.7% 15.5% 6.4% 100.0%

D= Diopter

Table 5. Preoperative Cycloplegic Refraction Stratified by Spherical Equivalentand Cylinder


SPHERICAL -1.00 to -2.00 to -3.00 to -4.00 to -5.00 to TOTALEQUIVALENT (D) -1.99 -2.99 -3.99 -4.99 -6.00

-1.O0 to -2.00 n/N 0/110 1/110 5/110 2/110 0/110 8/110% 0.0% 0.9% 4.5% 1.8% 0.0% 7.3%

0.O0 to -0.99 n/N 9/110 19/110 11/110 3/110 3/110 45/110% 8.2% 17.3% 10.0% 2.7% 2.7% 40.9%

+0.0! to +0.99 n/N 15/110 15/110 4/110 9/110 2/110 45/110% 13.6% 13.6% 3.6% 8.2% 1.8% 40.9%

n/N 0/110 2/110 5/110 3'110 2/110 12/110+1.00 to +2.00 210 1/1% 0.0% 1.8% 4.5% 2.7% 1.8% 10.9%

TOTAL 1n/N 24/110 37/110 25/110 17/110 7/110 110/110% 21.80% 33.6% 22.7% 15.5% 6.4% 100.0%

D= Diopter

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4. Key Effectiveness Outcomes

a) Summary Stratified by Visit and by Diopter

The key effectiveness outcomes for UCVA and accuracy of MRSE and manifest cylinder areshown by visit in Table 6. These parameters at 3 and 6 months are also shown stratified bypreoperative cycloplegic cylinder in Table 7 and by preoperative cycloplegic refraction sphericalequivalent (CRSE) in Table 8.

The effectiveness data meet the criteria established in the FDA Guidance Document for at least85% of eyes achieving a UCVA of 20/40 or better and accuracy of MRSE within 0.50D ofintended in at least 50% of eyes and within 1.00D in 75% of eyes at all postoperative intervals.

Table 6. Summary of Key Effectiveness Parameters Over TimeEffectiveness Parameters 1 MONTH 3 MONTHS 6 MONTHS 9 MONTHS

n/N 68/94 60/94 67/94 64/92U CVA 20/20 or better if72.3% 63.8% 71.3% 69.6%

CC (62.2, 81.1) (53.3, 73.5) (61.0, 80.1) (59.1, 78.7)n/N 70/110 62/110 70/110 66/108

UCVA 20/20 or better % 63.6% 56.4% 63.6% 61.1%C1 (53.9, 72.6) (46.6, 65.8) (53.9, 72.6) (51.3, 70.3)

n/N 95/110 89/110 96/110 91/108UCVA 20/25 or better % 86.4% 80.9% 87.3% 84.3%

CI (78.5, 92.2) (72.3, 87.8) (79.6, 92.9) (76.0, 90.6)n/N 106/110 105/110 108/110 101/108

UCVA 20/40 or better % 96.4% 95.5% 98.2% 93.5%Cl (91.0, 99.0) (89.7, 98.5) (93.6, 99.8) (87.1,97.4)

n/N 79/110 78/110 84/110 81/108MRSE + 0.50D of intended % 71.8% 70.9% 76.4% 75.0%

CI (62.4, 80.0) (61.5, 79.2) (67.3, 83.9) (65.7, 82.8)n/N 104/110 102/110 100/110 96/108

MRSE ±+ IOOD of intended % 94.5% 92.7% 90.9% 88.9%C[ (88.5, 98.0) (86.2, 96.8) (83.9, 95.6) (81.4, 94.1)

n/N 109/110 109/110 110/110 108/108MRSE ± 2.00D of intended % 99.1% 99.1% 100.0% 100.0%

Cl (95.0, 100.0) (95.0, 100.0) (96.7, 100.0) (96.6, 100.0)n/N 71/110 73/110 71/110 66/108% 64.5% 66.4% 64.5% 61.1%

of intended C1 (54.9, 73.4) (56.7, 75.1) (54.9, 73.4) (51.3, 70.3)

n/N 96/110 100/110 98/110 95/108% 87.3% 90.9% 89.1% 88.0%

of intended CI (79.6, 92.9) (83.9, 95.6) (81.7, 94.2) (80.3, 93.4)

n/N 108/110 109/110 109/110 107/108% 98.2% 99.1% 99.1% 99.1%

of intended I CI (93.6, 99.8) (95.0, 100, 100.0 ) , 100.0) (94.9, 100.0)

UCVA = Uncorrected Visual Acuity BSCVA = Best Spectacle Corrected Visual AcuityMRSE = Manifest Refraction Spherical Equivalent Cl = 95% Confidence Interval D = Diopter

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Table 7. Summary of Key Effectiveness Parameters at 3 and 6 MonthsStratified by Diopter (D) of Preoperative Cycloplegic Cylinder

_3 MONTHS _ ;

-1.00 to -2.00 to -3.00 to -4.00 to -5.00 to-1.99 -2.99 -3.99 -4.99 -6.00 Total

UCVA 20/20 or better if n/N 16/22 20/36 18/23 5/9 1/4 60/94Preop BSCVA 20/20 or better % 72.7% 55.6% 78.3% 55.6% 25.0% 63.8%

UCVA 20/20 or better n/N 16/24 21/37 18/25 6/17 1/7 62/110% 66.7% 56.8% 72.0% 35.3% 14.3% 56.4%

n/N 24/24 28/37 23/25 12/17 2/7 89/110% 100.0% 75.7% 92.0% 70.6% 28.6% 80.9%

IJCVA 20/40 or better n/N 24/24 33/37 25/25 17/17 6/7 105/110% 100.0% 89.2% 100.0% 100.0% 85.7% 95.5%

MRSE ± OSOD of intended n/N 23/24 25/37 17/25 9/17 4/7 78/110% 95.8% 67.6% 68.0% 52.9% 57.1% 70.9%

n/N 24/24 35/37 23/25 14/17 6/7 102/110% 100.0% 94.6% 92.0% 82.4% 85.7% 92.7%

MRSE ± 2.00D of intended n 24/24 37/37 25/25 16/17 7/7 109/110% 100.0% 100.0% 100.0% 94.1% 100.0% 99.1%

Cylinder magnitude < 0.50D n/N 20/24 25/37 14/25 13/17 1/7 73/110of intended % 83.3% 67.6% 56.0% 76.5% 14.3% 66.4%Cylinder magnitude < LOOD n/N 24/24 36/37 23/25 14/17 3/7 100/110of intended % 100.0% 97.3% 92.0% 82.4% 42.9% 90.9%Cylinder magnitude < 2.00D n/N 24/24 37/37 25/25 17/17 6/7 109/110of intended % 100.0% 100.0% 100.0% 100.0% 85.7% 99.1%

6 MoNTHs-1.00 to -2.00 to -3.00 to -4.00 to -5.00 to

-1.99 -2.99 -3.99 -4.99 -6.00 TotalUCVA 20/20 or better if n/N 21/22 19/36 20/23 7/9 0/4 67/94Preop BSCVA 20/20 or better % 95.5% 52.8% 87.0% 77.8% 0.0% 71.3%

UCVA 20/20 or better n/N 21/24 20/37 20/25 9/17 0/7 70/110% 87.5% 54.1% 80.0% 52.9% 0.0% 63.6%

n/N 24/24 29/37 25/25 14/17 4/7 96/110UCVA 20/25 or better % 100.0% 78.4% 100.0% 82.4% 57.1% 87.3%

UCVA 20/40 or better n/N 24/24 35/37 25/25 17/17 7/7 108/110% 100.0% 94.6% 100.0% 100.0% 100.0% 98.2%

MRSE ± 0O50D of intended n/N 24/24 28/37 18/25 10/17 4/7 84/110% 100.0% 75.7% 72.0% 58.8% 57.1% 76.4%

MRSE ± I .OOD of intended n/N 24/24 34/37 22/25 14/17 6/7 100/110% 100.0% 91.9% 88.0% 82.4% 85.7% 90.9%

n/N 24/24 37/37 25/25 17/17 7/7 110/110MRSE ± 2.OOD of intended % 100.0% 100.0% 100.0% 100.0% 100.0% 100.0%

Cylinder magnitude < 0.50D n/N 19/24 24/37 15/25 11/17 2/7 71/110of intended % 79.2% 64.9% 60.0% 64.7% 28.6% 64.5%Cylinder magnitude < l.OOD n/N 23/24 35/37 24/25 14/17 2/7 98/110of intended % 95.8% 94.6% 96.0% 82.4% 28.6% 89.1%Cylinder magnitude < 2.00D n/N 24/24 37/37 25/25 17/17 6/7 109/110of intended % 100.0% 100.0% 100.0% 100.0% 85.7% 99.1%

UCVA = Uncorrected Visual Acuity BSCVA = Best Spectacle Corrected Visual AcuityMRSE = Manifest Refraction Spherical Equivalent D = Diopter

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Table 8. Summary of Key Effectiveness Parameters at 3 and 6 MonthsStratified by Diopter (D) of Preoperative Cycloplegic Refraction Spherical Equivalent

_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 3M O NTH s _ _ _ _ _ _ _ _ _

Effectivness Paameters-1.00 to 0.00 to +0.01 to +1.00 to ToaEffectiveness Parameters -2.00 -0.99 +0.99 +2.00 Toa

UCVA 20/20 or better if n/N 516 24/41 24/36 7/11 60/94Preop BSCVA 20/20 or better % 83.3% 58.5% 66.7% 63.6% 63.8%

UCVA 2/20 orbettern/N 518 24/45 26/45 7/12 62/110UCVA 20/20 or better % 62.5% 53.3% 57.8% 58.3% 56.4%IUCVA 2/25 orbettern/N 7/8 39/45 34/45, 9/12 89/110UCVA 20/25 or better 87.5% 86.7% 75.6% 75.0% 80.9%U[CVA 2/40 orbettern/N 8/8 43/45 43/45 11/12 105/110UCVA 20/40 or better ¾ 100.0% 95.6% 95.6% 91.7% 95.5%MRSE± 0.0D o intnded n/N 7/8 35/45 27/45 9/12 78/110MRSE ± OOD of inended 4% 87.5% 77.8% 60.0% 75.0% 70.9%MRSE± 1.0D o intnded n/N 8/8 42/45 41/45 11/12 102/110MRSE ± lOODof intended% 100.0% 93.3% 91.1% 91.7% 92.7%

MRSE ± 2.OOD of intended n/N 8/8 45/45 44/45 12/12 109/110________________________ % 100.0% 100.0% 97.8% 100.0% 99.1%

Cylinder magnitude • OSO0D n/N 4/8 30/45 32/45 7/12 73/110of intended % 50.0% 66.7% 71.1% 58.3% 66.4%Cylinder magnitude < I .00D3 n/N 8/8 40/45 42/45 10/12 100/110of intended % 100.0% 88.9% 93.3% 83.3% 90.9%Cylinder magnitude < 2.OOD) n/N 8/8 44/45 45/45 12/12 109/110of intended % 100.0% 197.8% 100.0% 100.0% 99.1%

_____ ____ _____ ____ ____ 6 M ONTHS

Effectivenes Parameters-1.00 to 0.00 to +0.01 to +1.00 to TtaEffectiveness Parameters 2.00 -099 +0.99 +2.00 Toa

UCVA 20/20 or better if n/N 5/6 29/41I 27/36 6/11 67/94Preop BSCVA 20/20 or better % 83.3% 70.7% 75.0% 54.5% 71.3%

UCVA 20/20 or better n/N 6/8 29/45 29/45 6/12 70/110________________________ % 75.0% 64.4% 64.4% 50.0% 63.6%

UCVA 20/25 or better n/N 8/8 41/45 36/45 11/12 96/110________________________ % 100.0% 91.1% 80.0% 91.7% 87.3%

UCVA 20/40 or better n/ 88 444 45/45 11/12 108/110_________________________ % 100.0% 97.% 100.0% 91.7% 98.2%

MRSE ± OSO0D of intended n/N 7/8 34/45 34/45 9/12 84/110% 87.5% 75.6% 75.6% 75.0% 76.4%

MRSE ± IlOOD of intended n/N 8/8 42/45 39/45 11/12 100/110% 100.0% 93.3% 86.7% 91.7% 90.9%

MRSE ± 2.OOD of intended flN 8/8 45/45 45/45 12/12 110/110_________________________ % 100.0% 100.0% 100.0% 100.0% 100.0%

Cylinder magnitude • OSO0D n/N 4/8 27/45 33/45 7/12 71/110of intended % 50.0% 60.0% 73.3% 58.3% 64.5%Cylinder magnitude < lOOD1 n/N 8/8 39/45 42/45 9/12 98/110of intended % 100.0% 86.7% 93.3% 75.0% 89.1%Cylinder magnitude < 2.OOD) n/N 8/8 44/45 45/45 t12/12 109/1110of intended % 0 0.0%O/ 97.8% 100.0% 100.0% 99.1%

UCVA = Uncorrected Visual Acuity BSCVA = Best Spectacle Corrected Visual AcuityMRSE = Manifest Refraction Spherical Equivalent D = Diopter7260-0105 Rev. A of 52


b) Uncorrected Visual Acuity

Uncorrected visual acuity is displayed in Table 9. Preoperatively, 35.5% of eyes had a UCVA of20/40 or better. At 3 months, the UCVA was 20/20 or better in 56.4% of eyes, 20/25 or better in80.9% and 20/40 or better in 95.5%. At 6 months, the UCVA was 20/20 or better in 63.6% ofeyes, 20/25 or better in 87.3% and 20/40 or better in 98.2%. For those eyes with a preoperativeBSCVA of 20/20 or better, a UCVA of 20/20 or better was achieved in 63.8% and 71.3% of eyesat 3 and 6 months, respectively.

Table 9. Cumulative Uncorrected Visual Acuity at Distance

PREOP 1 MONTH. 3 MONTHS 6 MONTHS: 9 MONTHS

n/N 0/110 1/110 2/110 3/110 3/108% 0.0% 0.9% 1.8% 2.7% 2.8%n/N 0/110 8/110 11/110 11/110 9/108% 0.0% 7.3% 10.0% 10.0% 8.3%n/N 0/110 33/110 33/110 39/110 40/108% 2 b0.0% 30.0% 30.0% 35.5% 37.0%n/N 1/110 70/110 62/110 70/110 66/108% 0.9% 63.6% 56.4% 63.6% 61.1%n/N 4/110 95/110 89/110 96/110 91/108% 3.6% 86.4% 80.9% 87.3% 84.3%n/N 17/110 104/110 98/110 104/110 99/108% 15.5% 94.5% 89.1% 94.5% 91.7%n/N 39/110 106/110 105/110 108/110 101/108

20/40 or better % 35.5% 96.4% 95.5% 98.2% 93.5%

n/N 53/11 0 109/110 110/110 109/110 107/108% 48.2% 99.1% 100.0% 99.1% 99.1%n/N 68/110 110/10 110/110 110/110 107/108

20/63 or better % 61.8% 100.0% 100.0% 100.0% 99.1%

n/N 84/110 110/110 110/110 110/110 108/108% 76.4% 100.0% 100.0% 100.0% 100.0%n/N 98/110 110/110 110/110 110/110 108/108

20/1%00 or better 89.1% 100.0% 100.0% 100.0% 100.0%

n/N 12/110 0/110 0/110 0/110 0/108% 10.9% 0.0% 0.0% 0.0% 0.0%

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c) Comparison of Postoperative Uncorrected Visual Acuity and Preoperative BestSpectacle Corrected Visual Acuity

A comparison of postoperative UCVA to preoperative BSCVA after CustomCornea® LASIKsurgery is presented in Table 10 with differences based on lines of visual acuity. A postoperativeUCVA equal to or better than the preoperative BSCVA was achieved in 56.4% and 60.0% ofeyes at 3 and 6 months, respectively.

Table 10. Postoperative Uncorrected Visual Acuity Compared toPreoperative Best Spectacle Corrected Visual'Acuity

1 MONTH 3 MONThS 6 MONTHS 9 MONTHS

UCVA 2 Lines Better n/N 0/110 0/110 2/110 2/108Than Preop BSCVA % 0.0% 0.0% 1.8% 1.9%UCVA I Line Better n/N 13/110 18/110 19/110 20/108Than Preop BSCVA % 11.8% 16.4% 17.3% 18.5%UCVA Equal* to n/N 53/110 44/110 45/110 43/108Preop BSCVA % 48.2% 40.0% 40.9% 39.8%UCVA I Line Worse n/N 26/110 21/110 29/110 21/108Than Preop BSCVA % 23.6% 19.1% 26.4% 19.4%UCVA 2 Lines Worse n/N 9/110 13/110 7/110 11/108Than Preop BSCVA % 8.2% 11.8% 6.4% 10.2%UCVA >2 Lines Worse n/N 9/110 14/110 8/110 11/108Than Preop BSCVA % 8.2% 12.7% 7.3% 10.2%

UCVA = Uncorrected Visual Acuity BSCVA = Best Spectacle Corrected Visual AcuityEqual visual acuity is within 2 or 3 letters on the same line of a visual acuity chart

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d) Accuracy of Manifest Refraction Spherical Equivalent

As shown in Table I1, accuracy of MRSE was within 0.50D of emmetropia in 70.9% of eyes,within 1.00D in 92.7% and within 2.OOD in 99.1% at 3 months. At 6 months, the MRSE waswithin 0.50D of emmetropia in 76.4% of eyes, within 1.00D in 90.9% and within 2.OOD in100%. Of the eyes that did not achieve an MRSE within 1.00D of emmetropia, 5.5% at 3months and 7.3% at 6 months had more than +1.00D of hyperopia, whereas 1.8% at 3 and 6months had more than -1.00D of myopia. One eye (0.9%) had more than +2.OOD of hyperopia byMRSE at 3 months.

Table 11. Accuracy of Manifest Refraction Spherical Equivalent

IMONTH 3 MoN s 6.MONTHS 9 0MONTHs

* 0.50D n/N 79/110 78/110 84/110 81/108% 71.8% 70.9% 76.4% 75.0%

n/N 104/110 102/110 100/110 96/108% 94.5% 92.7% 90.9% 88.9%

n/N 109/110 109/110 110/110 108/108% 99.1% 99.1% 100.0% 100.0%

n/N 1/110 1/110 0/110 0/108% 0.9% 0.9% 0.0% 0.0%

n/N 5/110 6/110 8/110 9/108Postop Hyperopic MRSE > +I.00D 5 5 .%83% 4.5% 5.5% 7.3% 8.3%

n/N 1/110 1/110 0/110 0/108Postop Hyperopic MRSE > +2.000 D .%09 .%00% 0.9% 0.9% 0.0% 0.0%

n/N 1/110 2/110 2/110 3/108% 0.9% 1.8% 1.8% 2.8%

n/N 0/110 0/110 0/110 0/108Postop Myopic MRSE < -2.00D .%00 .%00% 0.0% 0.0% 0.0% 0.0%

MRSE = Manifest Refraction Spherical Equivalent D = Diopter

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e) Accuracy of Manifest Refraction by Meridian

Accuracy of manifest refraction is displayed for the preoperative hyperopic meridian in Table 12and for the preoperative myopic meridian in Table 13. Slight undercorrection along thepreoperative hyperopic meridian was observed based on a mean correction error of +0.15D+ 0.69D at 3 months and +0.20D ± 0.63D at 6 months. Along the preoperative myopic meridian,slight undercorrection was observed based on a mean correction error of -0.09D + 0.67D at3 months and -0.07D ± 0.61D at 6 months.

Table 12. Accuracy of Manifest Refraction in Preoperative Hyperopic MeridianCorrection Error 1 MONTH 3 MONTHS .6 MONs 9 MONTHS

Mean ± SD (D) +0.07 ± 0.68 +0.15 ± 0.69 +0.20 ± 0.63 +0.17 ± 0.63

n/N ± 050D79/110 74/110 77/110 73/1080 0% 71.8% 67.3% 70.0% 67.6%

Undercorrected (Postoperative Hyperopia) : :n/N 10/110 18/110 16/110 15/108% 9.1% 16.4% 14.5% 13.9%

n/N 4/110 7/110 8/110 7/108% 3.6% 6.4% 7.3% 6.5%

n/N 2/110 2/110 2/110 2/108% 1.8% 1.8% 1.8% 1.9%

Overcorrected (Postoperative Myopia)n/N 10/110 5/110 5/110 10/108

> 0.50 to lOD % 9.1% 4.5% 4.5% 9.3%n/N 5/110 4/1110 2/110 1/108> 1.00 to 2.OOD% 4.5% 3.6% 1.8% 0.9%

> 2.OOD) n/N 0/110 0/110 0/110 0/108% 0.0% 0.0% 0.0% 0.0%

Table 13. Accuracy of Manifest Refraction in Preoperative Myopic MeridianCorrection Error I MONTH 3 MONTHS 6 MONTHS 9 MONTHSMean ± SD (D) -0.12 ± 0.64 -0.09 4- 0.67 -0.07 ± 0.61 -0.13 ± 0.66

n/N~ 73/110 67/110 71/110 66/1080.00 ± 0.50D % 66.4% 60.9% 64.5% 61.1%Undercorrected (Postoperative Myopia)

n/N 17/110 20/110 17/110 19/108% 15.5% 18.2% 15.5% 17.6%

n/N 6/110 5/110 5/110 6/108% 5.5% 4.5% 4.5% 5.6%

> 2.OOD) n/N 1/110 0/110 0/110 0/108_________________ 0.9% 0.0% 0.0% 0.0%

Overcorrected (Postoperative Hyperopia)n/N 9/I 10 11/110 8/110 10/108

>0.50 to 1.00D % 8.2% 10.0% 7.3% 9.3%n/N 4/110 7/110 9/110 7/108% 3.6% 6.4% 8.2% 6.5%

n/N 0/110 0/110 0/110 0/108% 0.0% 0.0% 0.0% 0.0%

SD = Standard Deviation D = Diopter

7260-0105 Rev. A of 52 7,


f) Accuracy of Manifest Refraction Sphere and Cylinder Magnitude

Table 14 displays the accuracy of manifest sphere and cylinder magnitude. Postoperativemanifest sphere was within 0.50D of emmetropia in 71.3% of eyes, within 1.OOD3 in 87.0% andwithin 2.OOD in 98.1% at 3 months. Manifest sphere was within O.50D of emmetropia in 70.4%of eyes, within 1.OOD in 88.0% and within 2.O0D in 98. 1% at 6 months.

Postoperative manifest cylinder magnitude was < 0.50D of emnmetropia in 66.4% of eyes,CS lOOD in 90.9% and < 2.OOD in 99.1% at 3 months. Cylinder magnitude was < 0.50D in64.5% of eyes, < I .OOD in 89.1% and •<2.00D3 in 99.1% at 6 months.

Table 14. Accuracy of Manifest Sphere and Cylinder Magnitude

1 MONTH 3 MONTHmS 6 MONTHS 9 MONTHSSphere* (P4=108) (N4=1I08),' (N=108) (Nj106

Postop Mean ± SD (D) +0.27 ± 0.65 ±0.31 ± 0.68 +0.35 ± 0.62 +0.33 ± 0.64

Attempted Mean ± SD0(D) +1.20+±0.88 ±1.20+±0.88 +1.20 ± 0.88 +1.19 ±0.89

Achieved Mean ± SD (0) +0.92 ± 0.98 ±0.89 ± 1.03 +0.85 + 1.00 +0.87 ± 1.04

% Achieved 69+±85 64 ±79 61 ±85 60 ±91± 0.500 n/N 81/108 77/108 76/108 77/106

__________________ 75.0% 71.3% 70.4% 72.6%± 1.00D n/N 99/108 94/108 95/108 94/106

____ ____ ___ ____ ___ 91.7% 87.0% 88.0% 88.7%± 2.OOD n/N 106/108 106/108 106/108 104/106

___________________ 98.1% 98.1% 98.1% 98.1%I MONTH 3 MONTHS 6 MONTHS 9 MONTHSCylinder (N=110) (N=l1O) (N=110) .fNj128j

Postop Mean ± SD (D) -0.58 ± 0.55 -0.53 ± 0.53 -0.55 ± 0.47 -0.59 ± 0.46

Attempted Mean ± SD (D) -2.89 ± 1.21 -2.89+± 1.21 -2.89+± 1.21 -2.90 ± 1.21

Achieved Mean ± SD (D) -2.30 ± 1.12 -2.36 ± 1.12 -2.34 + 1.15 -2.31 ± 1.17

% Achieved 78 ±20 81 ±18 79+±18 77 ±20

• 0.50D ~ n/IN 71/I110 73/110 71/1 10 66/108SOSOD ~~~% 64.5% 66.4% 64.5% 61.1%

• 1.000 n/N 96/110 100/110 98/I110 95/108___________________ 87.3% 90.9% 89.1% 88.0%

< 2000D n/N 108/110 109/1 10 109/110 107/108_____ _____ _____ _____ 98.2% 99.1% 99.1%991

Excludes two eyes with a preoperative manifest sphere of OD.

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g) Effectiveness of Astigmatism Correction

Effectiveness of astigmatism correction at 3 and 6 months was evaluated based on the percentagereduction in cylinder magnitude and by vector analysis (Table 15). The mean percentagereduction in absolute manifest cylinder was 80.6% at 3 months and 79.1% at 6 months with anoverall trend for a greater percentage reduction in eyes with higher preoperative cylinder. Themean correction ratio based on vector analysis of manifest cylinder was 0.92 at 3 months and0.91 at 6 months.

Table 15. Effectiveness of Astigmatic Correction By Manifest Cylinder

3 MONTHS

Preoperative Mean Percentage Reduction Vector AnalysisCylinder N in Cylinder Magnitude Mean ± SD Correction Ratio

All 110 80.6% 0.92 ± 0.181.00 to < 2.00D 26 75.9% 0.86 ± 0.212.00 to < 3.00D 34 79.9% 0.94 ± 0.173.00 to < 4.00D 26 84.1% 0.93 +0.144.00 to < 5.00D 16 87.1% 1.01±0.125.00 to 6.00D 8 74.4% 0.83 ± 0.24

6 MONTHSPreoperative N Mean Percentage Reduction Vector Analysis

Cylinder in Cylinder Magnitude Mean + SD Correction RatioAll 110 79.1% 0.91 ± 0.17

1.00 to < 2.OOD 26 72.3% 0.84 ± 0.202.00 to < 3.00D 34 77.3% 0.92 ± 0.17~.00 to <4.OOD 26 83.9% 0.93 + 0.164.00 to < 5.OOD 16 87.0% 0.98 ± 0.125.00 to 6.00D 8 78.0% 0.86 ± 0.20

SD = Standard Deviation D = DiopterCorrection Ratio is the ratio of achieved vs. intended vector magnitude

7260-0105 Rev. A of 52


h) Refraction Over Time

Table 16 presents the manifest and cycloplegic phoropter refraction over time and the wavefrontrefraction from the wavefront measurement under cycloplegic conditions.

The mean manifest spherical equivalent was +0.03D ± 0.62D at 3 months and +0.06D ± 0.57D at6 months. The mean cycloplegic and wavefront spherical equivalents were similar over time.As expected under cycloplegic conditions, the cycloplegic and wavefront spherical equivalentsreflected more hyperopia that was within 0.50D of the manifest spherical equivalentpreoperatively and postoperatively.

The mean manifest cylinder was -0.53D ±- 0.53D at 3 months and -0.55D ± 0.47D at 6 months.The mean cycloplegic cylinder was similar to the manifest cylinder over time. The meanwavefront cylinder was within 0.25D of the manifest and cycloplegic refractions postoperatively.

Table 16. Mean Refraction Over Time

Mean 4- Standard Deviation PREOP I MONTH 3 MONTHS 6 MONTHS 9 MONTHSManifest Refraction (D) N=1 10 N-110 N=1 10 N=1 10 N=108Spherical Equivalent -0.27 ± 0.67 -0.03 ± 0.59 0.03 + 0.62 0.06 + 0.57 0.02 + 0.59Cylinder -2.89 ± 1.21 -0.58 ± 0.55 -0.53 ± 0.53 -0.55 ± 0.47 -0.59 ± 0.46Cycloplegic Refraction (D)* N=1 10 -- N1 10 N=108 --

Spherical Equivalent 0.06 + 0.65 -- 0.49 + 0.56 0.44 : 0.56 --

Cylinder -2.90 + 1.20 -- -0.49 + 0.51 -0.52 + 0.49 --

Wavefront Refraction (D)** N=1 10 N=103 N=100 N=103 N=I00Spherical Equivalent 0.04 ± 0.71 0.35 ± 0.45 0.44 ± 0.46 0.31 ± 0.46 0.39 ± 0.52Cylinder -2.91 : 1.25 -0.71 - 0.49 -0.69 ± 0.47 -0.65 · 0.35 -0.74 ± 0.52

Refractions at the spectacle plane D = Diopter· Cycloplegic refraction not required at 1 month and 9 months·* Wavefront measurement under cycloplegic conditions with refraction analyzed over 3.5mm diameter

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5. Stability of Manifest Refraction

Refractive stability was analyzed as paired differences in the non-vector manifest cylindermagnitude between consecutive visits (Table 17). Eyes with data available at each postoperativeinterval were evaluated in a 6-month consistent cohort of 110 eyes and a 9-month cohort of108 eyes.

Cylinder stability was achieved between I and 3 months with 100% of eyes demonstrating< L.OOD magnitude change and a mean change of -0.05D ± 0.29D at a rate of -0.03D change permonth for the 6-month consistent cohort. Cylinder stability was confirmed between 3 and6 months with 100% of eyes demonstrating < 1.00D magnitude change and a decrease in themean change over time to 0.02D ± 0.24D at a rate of 0.01D change per month. The 95%confidence interval of the mean change in cylinder magnitude overlapped between postoperativeintervals with a narrow range (< 0. I D) between the upper and lower limits.

The 9-month consistent cohort supported the overall trends in cylinder stability observed amongthe 6-month cohort. Between all consecutive postoperative intervals, at least 99.1% of eyesshowed •< 1.OOD of cylinder magnitude change. The mean change in cylinder magnitude was0.05D ± 0.25D between 6 and 9 months at a rate of 0.02D change per month.

Table 17. Stability of Manifest Cylinder Magnitude

Change in Cylinder Magnitude Between I and 3 Months 3 and 6 Monthsn/N 110/110 110/110

6-Month _< 1.O0D % 100.0% 100.0%Cohort(NAI 10) Mean Change* + Standard Deviation -0.05 ± 0.29 0.02 ± 0.24

95% Confidence Interval of Mean Change (-0.11, 0.00) (-0.03, 0.06)Mean Change* per Month -0.03 0.01

Change in Cylinder Magnitude Between I and 3 Months 3 and 6 Months 6 and 9 MonthsnfN 108/108 108/108 107/108.9-Month •< l.O0D % 100.0% 100.0% 99.1%

Cohort _______(Noh0r) Mean Change* ± Standard Deviation -0.05 ± 0.29 0.01 ± 0.23 0.05 ± 0.2595% Confidence Interval of Mean Change (-0.11, 0.00) (-0.03, 0.05) (0.00, 0.10)Mean Change* per Month -0.03 0.003 0.02

D = Diopter· Positive value reflects an increase in magnitude and a negative value reflects a decrease in magnitude

between visits.

7260-0105 Rev. A of 52 77


Similarly, refractive stability was analyzed as paired differences in MRSE between consecutivevisits for the 6-month and 9-month consistent cohorts of eyes with data available at eachpostoperative interval (Table 18).

Stability of MRSE was achieved between I and 3 months with 100% of eyes demonstrating achange in MRSE •< IOOD and a mean change of 0.06D + 0.29D at a rate of 0.03D change permonth for the 6-month consistent cohort. Stability was confirmed between 3 and 6 months with100% of eyes demonstrating a change in MRSE < 1.OOD and a decrease in the mean change overtime to 0.03D ± 0.25D at a rate of 0.0ID change per month. The 95% confidence interval of themean change in MRSE overlapped between postoperative intervals With a narrow range(_< 0.1 ID) between the upper and lower limits.

The 9-month consistent cohort showed similar MRSE stability trends to the 6-month cohort. Alleyes demonstrated a change in MRSE •< I.00D between postoperative visits. Between 6 and9 months, the mean MRSE change was -0.04D ± 0.26D at a rate of -0.0 ID change per month.

Table 18. Stability of Manifest Refraction Spherical Equivalent

Change in MRSE Between I and 3 Months 3 and 6 Monthsn/N 110/110 110/1106-Month < i.OOD % 100.0% 100.0%

Cohort(N-I 10) Mean Change I Standard Deviation 0.06 ± 0.29 0.03 ± 0.25

95% Confidence Interval of Mean Change (0.00, 0.11) (-0.01, 0.08)Mean Change per Month 0.03 0.01Change in MRSE Between I and 3 Months 3 and 6 Months 6 and 9 Months

n/N 108/108 108/108 108/1089-Month < i.OOD % 100.0% 100.0% 100.0%Cohort -0.04(N=s08) Mean Change ± Standard Deviation 0.06 ± 0.29 0.03 ± 0.25 -0.04 + 0.26

95% Confidence Interval of Mean Change (0.00, 0.11) (-0.02, 0.07) (-0.09, 0.01)Mean Change per Month 0.03 0.01 -0.01

D = Diopter

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6. Wavefront Outcomes

Table 19 displays the mean change from preoperative in total root mean square (RMS) wavefronterror and in higher-order aberrations through 6"' order. The mean change in total RMSwavefiront error decreased by 64.1% at 3 months and 67.2% at 6 months from preoperative.Higher-order aberrations were not significantly changed from preoperative on average with anincrease of 2.3% at 3 months and 2.2% at 6 months. Spherical aberration decreased inmagnitude at 3 and 6 months from preoperative with a mean directional shift from positivespherical aberration preoperatively (0.233pm) towards slightly negative spherical aberration at3 months (-0003pum) and 6 months (-0007ptm).

Table 19. Mean Change in Aberrations Up to 6th Order From Preoperative*

____________________ ~~3 MONTHS (N=I00) 6MONTus (N103)

Aberration Mean Change Mean Change Mean Change Mean Change________________________ (pin) (% ) (gin) (% )

Total RMS Error -1.I 905 -64.1 -1.998 -67.2Higher-Order 0.010 2.3 0.010 2.2

Coma 0.030 12.5 0.034 13.9Trefoil 0.008 4.0 0.005 2.7

Spherical Aberration Magnitude t -0.114 -48.4 -0.101 -42.8Spherical Aberration Value t-0.236 -101.2 -0.240 -102.9

Secondary Astigmatism 0.073 92.8 0.066 84.3Tetrafonil 0.023 30.4 0.027 35.3

Combined 5th and 6tIh Order 0.037 49.5 0.035 46.6RMS = Root Mean Square Wavefront Analysis Diameter = 6.0mm* Positive change represents increase from preop; Negative change represents decrease from preopt Based on absolute spherical aberration magnitude t Based on signed spherical aberration value

At 3 and 6 months, 100% of eyes had a reduction in total RMS error from preoperative. Areduction in higher-order aberrations from preoperative was observed in 55.0% of eyes at3 months and 54.4% at 6 months (Table 20).

Table 20. Percentage of Eyes with Reduced Aberrations Up to 6t Order FromPreoperative

_____________________________ 3 MONTHS (N= 100) 6 MONTHS (N= 103)Aberration O/ Eyes with Reduction in Aberrations

Total RMS Error 100.0% 100.0%Higher-Order 55.0% 54.4%

Coma 48.0% 49.5%Trefoil 49.0% 45.6%

Spherical Aberration Magnitude t 80.0% 78.6%Secondary Astigmatism 18.0% 17.5%

Tetrafoil 32.0% 32.0%Combined 5"h and 6"1' Order 18.0% 17.5%

RMS =Root Mean Square Wavefront Analysis Diameter =6.0mm

t Reduction in absolute spherical aberration magnitude

7260-0105 Rev. A of 52


Wavefront-guided CustomCornea® LASIK was compared to the baseline established forConventional LASIK correction of mixed astigmatism using phoropter refraction for eyes treatedunder the same study protocol over the same preoperative cycloplegic refractive range of-1.00Dto -3.50D cylinder. Wavefront aberrations at 3 and 6 months were analyzed up to 4 th order forthe Comparison Cohort (Table 21).

Compared to Conventional eyes, CustomCornea® eyes showed:

* statistically significantly lower mean amplitudes of total RMS error, higher-orderaberrations, trefoil, spherical aberration magnitude, secondary astigmatism and tetrafoil at3 and 6 months postoperatively (t-test with unequal variance; p<0.05).

· greater mean decrease in total RMS error from preoperative at'3 and 6 months.

• a mean decrease in higher-order aberrations from preoperative compared to a meanincrease for Conventional eyes at 3 and 6 months.

Spherical aberration value for the CustomComea® eyes was positive preoperatively (0.235gm)and at 3 months (0.041pm) and 6 months (0.029gm). Similarly for the Conventional eyes,spherical aberration value was positive preoperatively (0.176pim) and at 3 months (0.099gm) and6 months (0.1 12pm).

Table 21. Mean Change in Aberrations Up to 4kh Order from Preoperative*:CustomCornea® vs. Conventional Comparison Cohort

3 MONTHSAberration CustomCornea®(N74) Conventional (N=26) p-

PM % [xm % Value §Total RMS Error -1.509 -62.2 -0.990 -39.8 <0.0001

Higher-Order -0.060 -13.7 0.199 51.3 <0.0001Coma -0.008 -3.3 0.108 55.7 0.1542Trefoil -0.021 -11.1 0.167 91.6 <0.0001

Spherical Aberration Magnitude t -0.132 -56.0 -0.016 -8.9 0.0167Spherical Aberration Value t -0.195 -82.8 -0.076 -43.4 0.1332

Secondary Astigmatism 0.046 62.3 0.086 98.8 0.0142Tetrafoil 0.021 30.3 0.048 51.9 0.0029

6 MONTHS

Aberration CustomCorneas(N- 81) Conventional (N=25) p_gtm % pm % Value §

Total RMS Error -1.534 -63.2 -0.985 -39.6 <0.0001Higher-Order -0.053 -12.0 0.232 59.8 <0.0001

Coma -0.010 -3.9 0.135 69.5 0.0905Trefoil -0.014 -7.7 0.160 88.1 0.0001

Spherical Aberration Magnitude t -0.120 -51.1 -0.008 -4.6 0.0224Spherical Aberration Value t: -0.206 -87.5 -0.064 -36.4 0.0421


RMS = Root Mean Square Wavefront Analysis Diameter = 6.0mm* Positive change represents increase from preop; Negative change represents decrease from preop4: Based on absolute spherical aberration magnitude t Based on signed spherical aberration value§ t-test with unequal variance for postoperative comparison between treatment types;

p<0.05 statistically significant, shown in bold of 52 7260-0105 Rev. A 2,


A vision simulation program was used to model the effect of mean higher-order aberrationmagnitudes at 3 months after wavefront-guided CustomCornea ® LASIK versus ConventionalLASIK. The CustomCornea® cohort is restricted to those eyes over a comparable preoperativecylinder range to all Conventional mixed astigmatic eyes treated in the study (-1.00D to -3.50D).The difference in image blurring is comparable to a defocus error difference of approximately0.110 (i.e., 0.100 for the CustomCornea® simulation and 0.21D for the Conventionalsimulation).

The following charts (Figure 1) provide an illustration of the appearance of the visual acuitychart with glasses or contact lenses after surgery. The charts show the difference in higher-orderaberrations present in the eye after CustomCornea® LASIK (left chart) and after ConventionalLASIK (right chart).

DO NOT REPRODUCE THE CHARTS BELOWFigure 1. Simulated chart images for the average higher-order aberrations at 3 months

after wavefront-guided surgery compared to after conventional surgery, based onwavefront over a 6 mm diameter pupil.

After CustomCornea®LASIK After Conventional LASIK

P V E: H R P V E H RE H V D F E H Y D F

N U Z F E N U Z F EU H N Z R UIZN Z R

D N E F P DM V [ FPF U E P Z f C P Z.

As shown in Table 22, more eyes had a reduction in higher-order aberrations afterCustomCornea® LASIK compared to after Conventional LASIK at 3 months (66.2% vs. 7.7%)and 6 months (61.7% vs. 8.0%).

Table 22. Percentage of Eyes with Reduced Aberrations Up to 4th Order from Preoperative:CustomCornea® vs. Conventional Comparison Cohort

3 MONTHS 6 MONTHSAberration CustomCornea® Conventional CustomCornea® Conventional

ON = 74) (N = 26) (N = 81) (N = 25)Total RMS Error 100.0% 92.3% 100.0% 96.0%

Higher-Order 66.2% 7.7% 61.7% 8.0%Coma 55.4% 19.2% 55.6% 28.0%

Trefoil 55.4% 7.7% 51.9% 20.0%Spherical Aberration Magnitudet 86.5% 57.7% 85.2% 52.0%

Secondary Astigmatism 21.6% 19.2% 19.8% 16.0%Tetrafoil 32.4% 23.1% 30.9% 20.0%

RMS = Root Mean Square Wavefront Analysis Diameter = 6.0mm

t Reduction in absolute spherical aberration magnitude7260-0105 Rev. A of 52


7. Key Safety Outcomes


The key safety outcomes are presented by visit in Table 23. These parameters at 3 and 6 monthsare also shown stratified by preoperative cycloplegic cylinder in Table 24 and by preoperativeCRSE in Table 25.

No eyes had a loss of more than 2 lines of BSCVA and one eye (0.9%) had a loss of 2 lines atI month. All eyes had a BSCVA within I line of preoperative BSCVA at 3 months or later.Preoperative BSCVA was 20/25 or better for all eyes. Postoperative BSCVA was 20/32 or betterat all postoperative intervals and 20/25 or better at 3 months or later.

The safety data meet the criteria established in the FDA Guidance Document of less than 5% ofeyes with a loss of more than 2 lines of BSCVA, less than 1% having a BSCVA of worse than20/40, and less than 5% having an increase in cylinder magnitude of more than 2D at allpostoperative intervals.

Table 23. Summary of Key Safety Parameters Over Time

Safety Parameters 1 MONTH 3 MONTHS 6 MONTHS 9 MONTHSn/N 0/110 0/110 0/110 0/108

Loss of> 2 Lines BSCVA % 0.0% 0.0% 0.0% 0.0%CI (0.0, 3.3) (0.0, 3.3) (0.0, 3.3) (0.0, 3.4)n/N 1/110 0/110 0/110 0/108

Loss of 2 Lines BSCVA % 0.9% 0.0% 0.0% 0.0%CI (0.0, 5.0) (0.0, 3.3) (0.0, 3.3) (0.0, 3.4)n/N 0/110 0/110 0/110 0/108

BSCVA worse than 20/40 % 0.0% 0.0% 0.0% 0.0%CI (0.0, 3.3) (0.0, 3.3) (0.0,3.3) (0.0, 3.4)nJN 0/110 0/110 0/110 0/108

Increase > 2D cylinder magnitude % 0.0% 0.0% 0.0% 0.0%CI (0.0, 3.3) (0.0, 3.3) (0.0, 3.3) (0.0, 3.4)n/N 1/94 0/94 0/94 0/92

BSCVA worse than 20/25 1/94 0/94 0/94 0/92if 20/20 or better preoperatively %

CI (0.0, 5.8) (0.0, 3.8) (0.0, 3.8) (0.0, 3.9)

BSCVA = Best Spectacle Corrected Visual Acuity CI = 95% Confidence Interval D = Diopter

of 52 7260-0105 Rev A


Table 24. Summary of Key Safety Parameters at 3 and 6 MonthsStratified by Diopter (D) of Preoperative Cycloplegic Cylinder

_______________ ~~3 MONTH-s _ _ _

-1.00 to -2.00 to -3.00 to -4.00 to -5.00 toSafety ParametersToa -1.99 -2.99 -3.99 -4.99 -6.00Loss of> 2 Lines BSCVA r/N 0/24 0/37 0/25 0/17 0/7 0/110

__________________________ % 0.0% 0.0% 0.0% 0.0% 0.0% 0.0%

Loss of 2 Lines BSCVA n/N 0/24 0/37 0/25 0/17 0/7 0/110% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0%

BC w4n/N 0/24 0/37 0/25 0/17 0/7 0/110% I00.0% 0.0% .0% 0.0%

n/N 0/24 0/37 0/25 0/17 0/7 0/110n s cn% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0%

BSCVA worse than 20/25 n/N 0/22 0/36 0/23 0/9 0/4 0/94if 20/20 or better preoperatively % 0.0% 0.0% 0.0% 0.0% 0.0% 0.0%

6 MONTHS _

Ss-1.00 to -2.00 to -3.00 to -4.00 to -5.00 to-1.99 -2.99 -3.99 -4.99 -6.00

Loss of > 2 Lines BSCVA n/N 0/24 0/37 0/25 0/17 0/7 0/110_________________________ % 0.0% 0.0% 0.0% 0.0% 0.0% 0.0%

Loss of 2 Lines BSCVA n/N 0/24 0/37 0/25 0/17 0/7 0/110_% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0%

BSCVA worse than 20/40 n/N 0/24 0/37 0/25 0/17 0/7 0/110_ _ __ % 0.0% 0.0% 0.0% 0.0% 0.0% 0.0%

n/N 0/24 0/37 0/25 0/17 0/7 0/110[Increase> 2D cylinder magnitude % 0.0% 0% 0.0% 0.0% 0.0% 0.0%

BSCVA worse than 20/25 n/N 0/22 0/36 0/23 0/9 0/4 0/94if 20/20 or better preoperatively % 0.0% 0.0% 0% 0.0% 0.0% 0.0%

BSCVA = Best Spectacle Corrected Visual Acuity D = Diopter

7260-0105 Rev. A of 52


Table 25. Summary of Key Safety Parameters at 3 and 6 MonthsStratified by Diopter (D) of Preoperative Cycloplegic Refraction Spherical Equivalent

_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 3 ~M O N TH S i AN _ _ _ _ _ _

Safety Parameters [ -1.00 to 0.00 to +0.01 to +1.00 to Total-2.00 -0.99 +0.99 +2.00

n/N 0/8 0/45 0/45 0/12 0/110Loss of >2 Lines BSCVA 0.0% 0.0% 0.0% 0.0% 0.0%

Loss of 2 Lines BSCVA n/N 0/8 0/45 0/45 0/12 0/110% 0.0% 0.0% 0.0% 0.0% 0.0%

n/N 0/8 0/45 0/45 0/12 0/110% 0.0% 0.0% 0.0% 0.0% 0.0%

n/N 0/8 0/45 0/45 0/12 0/110Increase> 2D cylinder magnitude % 0.0% 0.0% 0.0% 0.0% 0.0%

BSCVA worse than 20/25 n/N 0/6 0/41 0/36 0/11 0/94if 20/20 or better preoperatively % 0.0% 0.0% 0.0% 0.0% 0.0%

6 MONTHS-1.00 to 0.00 to +0.01 to +1.00 to

-2.00 -0.99 +0.99 +2.00 Total

Loss of > 2 Lines BSCVA n/N 0/8 0/45 0/45 0/12 0/110_______ _______ _______ ______ 0.0% 0.0% 0.0% .0.0% 0.0%


BSCVA worse than 20/40 n/N 0/8 0/45 0/45 0/12 0/110% 0.0% 0.0% 0.0% 0.0% 0.0%

n/N 0/8 0/45 0/45 0/12 0/110% 0.0% 0.0% 0.0% 0.0% 0.0%



of 52 7260-0105 Rev A


b) Change in Best Spectacle Corrected Visual Acuity

Using a standard (high-contrast) visual acuity chart, BSCVA was measured under dim roomillumination (10-12 cd/mr2). At least 90.9% of eyes had a gain or no change in BSCVA frompreoperative at all postoperative intervals (Table 26). A trend for postoperative BSCVA gain ofI line was observed compared to a loss of I line at 3 months (39.1% vs. 6.4%) and at 6 months(38.2% vs. 3.6%). While a small percentage of eyes had a BSCVA gain of 2 lines at 3 months(0.9%) and at 6 months (3.6%), no eyes had a BSCVA loss of 2 lines at 3 months or later.

Table 26. Change in Best Spectacle Corrected Visual Acuity?~'' ~..... . ivd~ft i~r~~ MORTI~t49bw~NTMNH? Z'MN~S

n/N 0/110 0/110 0/110 0/108Decrease > 2 Lines % 0.0% 0.0% 0.0% 0.0%

n/N 1/110 0/110 0/110 0/108Decrease 2 Lines % 0.9% 0.0% 0.0% 0.0%

n/N 9/110 7/110 4/110 6/108Derae ie% 8.2% 6.4% 3.6% 5.6%n/N 68/110 59/110 60/110 51/108% 61.8% 53.6% 54.5% 47.2%

n/N 29/110 43/110 42/110 48/108Increase I Line % 26.4% 39.1% 38.2% 44.4%

n/N 3/110 1/110 4/110 3/108Increase 2 Lines % 2.7% 0.9% 3.6% 2.8%

n/N 0/110 0/110 0/110 0/108% 0.0% 0.0% 0.0% 0.0%

Low contrast BSCVA was measured using a 10% low contrast visual acuity chart under dimroom illumination (Table 27). Slightly more eyes had a gain than loss of I line of low contrastBSCVA at 3 months (30.6% vs. 17.6%) and at 6 months (33.6% vs. 19.1%). In addition, moreeyes had a gain than loss ofŽ> 2 lines of Low contrast BSCVA at 3 months (7.4% vs. 4.6%) and6 months (8.2% vs. 2.7%).

Table 27. Change in Low Contrast Best Spectacle Corrected Visual Acuity

n/N 1/108 0/I 10Decrease > 2 Lines n 1/10 0/0%~~~~ 09% 0.0%n/N 4/108 3/110Decrease 2 Lines % 3.70 2.71% 3.7% 2.7%

in/N 19/108 21/110% 17.6% 19.1%

n/N 43/108 40/110% 39.8% 36.4%n/N 33/108 37/110Increase I Line % 30.6% 33.6%

n/N 7/108 8/110Increase 2 Lines % 6.5% 7.3%

n/N 1/108 1/11I0Increase > 2 Lines 0.9% 0.9%% 0.9' Ae9%

7260-0105 Rev. A of 52 ~


8. Change in Contrast Sensitivity

Contrast sensitivity was measured under both photopic and mesopic conditions using theCSV-1000 (VectorVision 9). A clinically significant change from preoperative level was definedas > 2 levels (> 0.3 log units) at two or more spatial frequencies (T[able 28).

The majority of eyes did not have a clinically significant change in contrast sensitivity frompreoperative to postoperative. Of the eyes with a change in photopic contrast sensitivity, slightlyfewer eyes showed a gain than loss at 3 months (2.7% vs. 6.4%) and an equal percentage of eyes(5.5%) had a gain or loss at 6 months. Under mesopic conditions, a trend for more eyes with again than loss of contrast sensitivity was observed at 3 months (22.4% vs. 11.2%) and at 6months (26.2% vs. 10.3%).

In addition, a gain from preoperative was observed in the mean contrast sensitivity log at eachspatial frequency under photopic and mesopic conditions at 3 and 6 months (Table 29). Whileno statistically significant change was observed at 3 months, statistically significant (p<O.05)gains were noted at 6 cycles per degree (cpd) under photopic conditions and for all spatialfrequencies under mesopic conditions at 6 months.

Table 28. Change of > 2 Levels (> 0.3 Lag) at 2 or More Spatial Frequencies

__________________ ~Photopic M csopic*______________ ~~3 MONTHS 6MOTIS 3 MONTH'S .' 64MON'THS

Loss ~~~~n/N 7/110 6/110 12/107 11/107Loss________ 6.4% 5.5% 11.2% 10.3%

No Change n/N 100/I 10 98/1 10 71/107 68/107No Change ~ ~ % 90.9% 89.1% 66.4% 63.6%

Gain n/N- 3/I10 6/110 24/107 28/107________________ 2.7% 5.5% 22.4% 26.2%

Table 29. Comparison of Mean Contrast Sensitivity Log by Spatial Frequency

Spatial Preop 3-Month vle -ot ivleFrequency (cpd) Mean d4 SD Mean + SD P-vaut Mean + SD vle

3 1.73+±0.15 1.75+±0.19 0.156 1.75 ±0.17 0A1156 1.92+±0.19 1.94+±0.25 0.204 1.96+±0.22 0.01812 1.56+±0.25 1.56+±0.28 0.986 I 57+±0.31 0.748

18 1.09+±0.26 1.08 ±0.31 0.764 1.08+±0.32 0.892

VWOMEMN_ MRIJAZU 0MVE__ W_ _ l7 _ _

3 1.51 ±+0.23 1.55 + 0.26 0.134 1.56 + 0.24 0.0366 1.48 + 0.25 1.52 + 0.28 0.238 1.56 ± 0.27 0.00912 0.91 ±+0.32 0.98 +E0.31 0.086 1.00 ±0.33 0.04818 0.41 ± 0.34 0.42+±0.36 0.749 0.50 ±0.36 0.016

*Mesopic illumination with neutral density filters in front of eyestp-value from paired t-est of differences between preoperative and postoperative means;

p < 0.05 is statistically significant, shown in bold

Vector Vision TM of Brain Lab AG 8 of 52 7260-0105 Rev. A


9. Patient Questionnaire

Patients were asked to rate symptoms without glasses or contact lenses after surgery as comparedto their recollection of symptoms before surgery, as shown in Table 30. The symptoms reportedas "worse" or "significantly worse" in >10% of eyes at 6 months were dryness, light sensitivity,blurring of vision, fluctuation of vision, glare, halos, and night driving difficulty.

Table 30. Postoperative Change in Subjective Symptoms without Correctionvs. Preoperative*

Significantly No SignificantlyComfort Symptoms Better Change Worse WorseBurning 0.0% 10.0% 86.4% 2.7% 0.9%Dryness 3.6% 7.3% 47.3% 40.0% 1.8%Excessive Tearing 1.8% 2.7% 95.5% 0.0% 0.0%Gritty Feeling 3.6% 5.5% 83.6% 6.4% 0.9%Headache 7.3% 17.3% 70.9% 4.5% 0.0%Light Sensitivity 10.9% 7.3% 54.5% 27.3% 0.0%Pain 4.5% 5.5% 81.8% 6.4% 1.8%Redness 0.0% 11.8% 81.8% 4.5% 1.8%Visual SymptomsBlurring of Vision 14.5% 17.3% 46.4% 20.0% 1.8%Double Vision 11.8% 8.2% 71.8% 8.2% 0.0%Fluctuation of Vision 5.5% 8.2% 62.7% 20.0% 3.6%Glare 10.9% 10.0% 52.7% 26.4% 0.0%Halos 8.2% 5.5% 59.1% 27.3% 0.0%Night Driving Difficulty 21.8% 10.0% 48.2% 20.0% 0.0%

.6 M O aTHS ,! 610);, Q rN--:6Significantly No SignificantlyComfort Symptoms B BetterBetter C a Worse

Burning 4.5% 9.1% 79.1% 6.4% 0.9%Dryness 5.5% 6.4% 49.1% 36.4% 2.7%Excessive Tearing 2.7% 4.5% 90.0% 2.7% 0.0%Gritty Feeling 2.7% 5.5% 84.5% 6.4% 0.9%Headache 9.1% 10.0% 76.4% 4.5% 0.0%Light Sensitivity 10.9% 11.8% 54.5% 20.9% 1.8%Pain 6.4% 4.5% 84.5% 4.5% 0.0%Redness 3.6% 7.3% 81.8% 7.3% 0.0%Visual SymptomsBlurring of Vision 13.6% 15.5% 49.1% 13.6% 8.2%Double Vision 7.3% 12.7% 73.6% 4.5% 1.8%Fluctuation of Vision 8.2% 10.0% 55.5% 21.8% 4.5%Glare 10.0% 8.2% 68.2% 13.6% 0.0%Halos 10.0% 3.6% 63.6% 19.1% 3.6%Night Driving Difficulty 19.1% 19.1% 47.3./o 10.9% 3.6%

Based on the patients' comparison of symptom severity after surgery as better or worse compared to theirrecollection of symptom sevedly before surgery.

7260-0105 Rev. A of 52 7


Compared to preoperative, uncorrected quality of vision at 6 months was reported as better orsignificantly better in 86.3% of eyes, same in 4.5% and worse or significantly worse in 9.1%(Table 3 1). Satisfaction with surgery at 6 months was reported as satisfied or extremely satisfiedin 73.7% of eyes, unsure in 10.9%, and unsatisfied or extremely unsatisfied in 15.4% (Table 32).Frequency of wearing distance correction at 6 months was reported as never in 81.8% of eyesand at least some of the time in 18.2% with frequent or constant use in 11.8% (Table 33).

Table 31. Postoperative Quality of Vision without Correctionvs. Preoperative*

Significantly Better 54.6% 52.7%Better 28.7% 33.6%Same 7.4% 4.5%

Worse 7.4% 5.5%

Significantly Worse 1.9% 3.6%

'Based on the patients' comparison of quality of vision after surgery as better or worsecompared to their recollection of quality of vision before surgery.

Table 32. Postoperative Satisfaction with Surgery

3 MONTHS 6MoNTiS

Extremely Satisfied 47.2% 48.2%

Satisfied 26.9% 25.5%

Not Sure 15.7% 10.9%

Unsatisfied 6.5% 11.8%

Extremely Unsatisfied 3.7% 3.6%

Table 33. Postoperative Frequency of Distance Correction

Never 85.2% 81.8%

Seldom 3.7% 6.4%Frequently 1.9% 1.8%

Constantly 9.3% l 0.0%

10. Retreatment

There are insufficient data for retreatment to establish safety and effectiveness.

of 52 7260-0105 Rev. A


11. Statistical Analysis Outcomes

Statistical analysis was performed to assess for potential associations between demographic andbaseline characteristics and clinical outcomes. Age, gender, race, preoperative cycloplegic cylinder,preoperative CRSE, operative room humidity and temperature were the characteristics considered tohave the most potential for clinical relevance to the procedure. Outcomes evaluated at refractivestability (3 months) and at 6 months included: BSCVA loss of_> 2 lines; UCVA of 20/20 or betterand 20/40 or better; and accuracy of MRSE, manifest sphere and manifest cylinder magnitude within0.50D and 1.00D of emmetropia.

One-sided exact binomial tests (u=0.05) were used to support the observed overall rates of safety andeffectiveness outcomes to the FDA Guidance Document targets. There was no BSCVA loss of> 2 lines at 3 and 6 months, thereby meeting the FDA target rate of< 5% of eyes with BSCVA lossof > 2 lines for safety. FDA targets were met or exceeded for effectiveness outcomes overall,including UCVA 20/40 or better and accuracy of MRSE within 0.50D and within 1.00D ofemmetropia. For each baseline subgroup, the observed rate either met the target or the 95%confidence interval (CI) contained the FDA target.

To assess the consistency of outcomes across characteristics, differences in rates among subgroupswere assessed using the Cochran-Mantel-Haenszel (CMH) test. No statistical significance wasobserved among subgroups of preoperative CRSE for any outcome. Statistically significant (p<0.05)trends among subgroups are listed below by characteristic.

Among age subgroups by decade over a range of 20 to 60 years, higher rates were observed inyounger patients as compared to older patients for the following outcomes:

* UCVA 20/20 or better at 3 months (p4).012 9 ). The observed rate was > 60.0% for subgroupsbetween 20 to 49 years vs. 33.3% for 50 to 60 years. At 6 months, no statistical significance remainedamong age subgroups for UCVA 20/20 or better.

* UCVA of 20/40 or better at 3 months (p-0.0 02 0). The observed rate was 100% for subgroupsbetween 20 to 49 years vs. 81.5% for 50 to 60 years, although the 95% CI contained the FDA targetof 85%. At 6 months, no statistical significance by age remained and all age subgroups exceeded theFDA target for UCVA of 20/40 or better.

* MRSE within 0.50D at 3 and 6 months (p=.01 14 and p=0.005 6 ). The observed rate was > 76.2% at3 and 6 months for subgroups between 20 to 49 years vs. 40.7% at 3 months and 51.9% at 6 monthsfor 50 to 60 years with the FDA target of 50% included in the 95% Cl. All age subgroups met orexceeded the FDA target for MRSS within 0.50D at 6 months.

* No statistical significance by age was observed for accuracy of MRSE within 1.00D and all agesubgroups met or exceeded the FDA target for MRSE within 1.00D at 3 and 6 months. However,older patients, primarily between 40 and 60 years, were more likely to have a hyperopic MRSE ofmore than +1.00D at 3 and 6 months (pA0.0108 and p=0.0013). Younger patients were more likely tohave a myopic MRSE of more than -1.00D at 3 and 6 months (p-0.039 1), which was observed in twoeyes of a 20 year-old patient.

* Manifest sphere within 0.50D at 3 and 6 months (p-0.0005 and p4).0027). The observed rate was> 71.4% for subgroups between 20 to 49 years vs. 37.0% for 50 to 60 years.

* Manifest sphere within 1.00D at 6 months (p=0.0005). The observed rate was > 91.4% for subgroupsbetween 20 to 49 years vs. 66.7% for 50 to 60 years. Older patients, primarily between 40 and60 years, were more likely to have a hyperopic manifest sphere of more than +1.00D at 3 and6 months (p=0.0042 and p=0.0005). Younger patients were more likely to have a myopic manifestsphere of more than -1.00D at 3 months (p=0.039 1), which was observed in two eyes of a 20 year-oldpatient.

7260-0105 Rev. ,A of52 9/


Preoperative astigmatism measured in subgroups by diopter of cycloplegic cylinder over a rangefrom -1.00D to -6.00D. Eyes with lower preoperative astigmatism showed higher rates ascompared to eyes with higher preoperative astigmatism for the following outcomes (observedrates at 3 and 6 months by preoperative cycloplegic cylinder are shown in Table 6):

* UCVA 20/20 or better at 3 and 6 months (p=0.0404 and p=0.0060). All preoperative cylindersubgroups met or exceeded the FDA target for UCVA of 20/40 or better at 3 and 6 months.

* MRSE within 0.50D at 3 and 6 months (p=0.0038 and p=0.0011). All preoperative cylindersubgroups met or exceeded the FDA target for MRSE within 0.50D.at 3 and 6 months.

• MRSE within 1.00D at 3 and 6 months (p=0.0304 and p=0.0433). All preoperative cylindersubgroups met or exceeded the FDA target for MRSE within 1.00D at 3 and 6 months.

* Manifest sphere within L.O0D at 3 months (p=0.0082). No statistical significance based onpreoperative cylinder remained for manifest sphere at 6 months. In addition, eyes with higherpreoperative astigmatism were more likely to have a hyperopic manifest sphere of more than +I.00Dat 3 months compared to eyes with lower preoperative astigmatism (pI0.0412).

* Manifest cylinder magnitude _< 0.50D at 3 months (p"0.02 2 7).

* Manifest cylinder magnitudes 1.00D at 3 and 6 months (p--0.0002 and p-0.0012).

Race was analyzed in two subgroups, 94.5% Caucasians and 5.5% other races, including Hispanic(3.6%) and Indian (1.8%). Note that apparent associations by race should be interpreted with cautionbecause of the small sample size of six eyes in the other races subgroup. Caucasians had higher ratesthan other races for the following outcomes:

· MRSE within O.5OD at 3 months (p=0.0380). The observed rate was 73.1% for Caucasians vs. two ofsix eyes (33.3%) in the other races subgroup, although the 95% CI contained the FDA target of 50%.At 6 months, no statistically significant difference remained by race for MRSE within 0.50D. Bothsubgroups met or exceeded the FDA target for MRSE within 0.50D at 6 months and for MRSE within1.00D at 3 and 6 months.

* Manifest sphere within 0.50D at 6 months (p=0.0380). The observed rate was 73.1% for Caucasiansvs. two of six eyes (33.3%) in the other races subgroup.

* Manifest cylinder magnitude •< 1.00D at 3 months (p=0.03 4 5). The observed rate was 92.3% forCaucasians vs. four of six eyes (66.7%) in the other races subgroup. At 6 months, no statisticallysignificant difference based on race remained for manifest cylinder outcomes.

Room temperature, room humidity and gender each had one statistically significant association withpostoperative manifest sphere or manifest cylinder magnitude, as follows:

* Eyes treated in a room with a lower temperature between 65.00 F and 69.9°F showed higher rates thaneyes treated in a room between 70.00 F and 74.90 F for manifest sphere within 1.00D at 3 months(97.0% vs. 83.1%; p=0.04 6 7).

* Eyes treated in a lower room humidity showed higher rates as compared to eyes treated in higherroom humidity for manifest cylinder magnitude < 1.00D at 6 months (pAJ.0450). The observed ratewas > 81.3% for room humidity subgroups between 18% to 59% vs. 0.0% for the two eyes of onepatient treated in a room humidity of 63%.

· Females showed higher rates as compared to males for manifest cylinder magnitude < 1.00D at3 months (96.6% vs. 84.3%; pAJ.0260) and at 6 months (96.6% vs. 80.4%; p=0.0068).

of 52 7260-0105 Rev. A 92.


12. Comparative Analysis by Defocus Type

To optimize the CustomCornea® wavefront-guided LASIK treatment of mixed astigmatism, eyeswere categorized as myopic or hyperopic based on the preoperative wavefront defocus error. Myopicor hyperopic components of the algorithm were used as determined by the preoperative wavefrontdefocus. The study included 85 eyes with a myopic defocus and 25 eyes with a hyperopic defocusbased on the preoperative wavefront.

Clinical outcomes at 3 and 6 months for each preoperative wavefrortt defocus type were compared toestablished target rates for refractive surgery. In addition, outcomes were compared between myopicand hyperopic defocus types. Outcomes evaluated at refractive stability (3 months) and at 6 monthsincluded: BSCVA loss of Ž 2 lines; UCVA of 20/20 or better and 20/40 or better; and accuracy ofMRSE, manifest sphere and manifest cylinder magnitude within 0.50D and I .OOD of emmetropia.Postoperative outcomes of myopia or hyperopia of more than I .00D) by MRSE and manifest spherewere also evaluated.

One-sided exact binomial tests (cr0.05) were used to compare the observed overall rates of eyesmeeting safety and effectiveness criteria to the FDA Guidance Document target rates. There was noBSCVA loss of > 2 lines at 3 and 6 months for both subgroups, thereby meeting the FDA target rateof < 5% of eyes with BSCVA loss of > 2 lines for safety. Both defocus types of mixed astigmaticeyes exceeded FDA targets overall for effectiveness including for UCVA of 20/40 or better andaccuracy of MRSE within 0O50D and IGOD1 of emmetropia at 3 and 6 months.

To compare clinical outcomes of mixed astigmatic eyes by preoperative defocus type, the Cochran-Mantel-Haenszel (CMH) test was used to assess for differences. A p-value < 0.05 would indicate astatistically significant difference in outcomes between defocus types. Myopic and hyperopicdefocus groups had outcomes that were not significantly different. Tables 34 and 35 display thecomparative analysis by defocus type at 3 and 6 months.

7260-0105 Rev. A oft52 C3


Table 34. Comparative Analysis of Mixed Astigmatic Eyes by Defocus Typeat 3 Months

Criteria CMIH Myopic Hyperopic Ttl FDA TargetCriteria P-VNalue' Defocus IDefocus Ttl P-Value"

Key Effectiveness Parametersn/N 49/85 13/25 62/I10

UJCVA 20/20 or better 0.6183 % 57.6% 52.0% 56.4% -

_________________________ ~Cl (64683 (1.,72) (46.6, 65.8) _____

n/N 80/85 25/25 105/I 10UCVA 20/40 or better 0.2166 % 94.1% 100.0% 95.5% 099

Cl (86.8, 98.1) (86.3, 100.0) (89.7, 98.5) 0__9999__n/N 61/85 17/25 78/110 > 0

MRSF± 0.50D 0.7169 % 71.8% 68.0% 70.9% Ž0cl 79 ~~~~~~~1.0000

n/N 79/85 23/25 102/110 >75MRSFt lOOD01 0.8740 % 92.9% 92.0% 92.7% 100

_________ CI (85.3, 97.4) (74.0, 99.0) (86.2, 96.8) ________ I

Accuracy of Manifest Sphere and Cylinder _____

n/N 57/85 22/25 79/110Manifest Sphere ± 0O5OD 0.0417 % 67.1% 88.0% 71.8% -

CI (56.0, 76.9)- (68.8, 97.5) (62.4, 80.0)nIN 74/85 22/25 96/1 10

Manifest Sphere ± 1.001) 0.9017 .% 87.1% 88.0% 87.3% -

______________________ CI j7.0, 93.) (68.8 97.5) (79.6, 92.9)

Manifest Cylinder Magnituden/N 55/85 18/25 73/110Maifs0Cyi50rManiud 0.4994 % 64.7% 72.0% 66.4% -

< 0.50D ~~~~~~~CI 536_48 5.,8.) (56.7 75.1)

Manifest Cylinder Magnituden/N 79/85 21/25 100/110MaifstClideOagiDd 0.1736 % 92.9% 84.0% 90.9%

< 1.00D I ~~~~~~CI (85.3, 97.4) (63.9, 95.5) (83.9, 95.6)Postoperative Manifest Spherical Equivalent and Manifet Sphere

Postoperative MRSE n/N 6/85 0/25 6/110> +1001 (Hyeroic)0.1738 % 7.1% 0.0% 5.5% -

> +1.OOD (Hyperopic) Cl ~~~(2.6, 14.7) (0.0, 13.7) (2.0, 11.5) _____

Postoperative MRSE n/N 0/85 2/25 2/110< -1.013 (Mopic)0.0088 % 0.0% 8.0% 1.8% -

<-1.OOD(Myopic) Cl (0.0,4.2) (1.0,26.0) ~~(0.2,6.4)Postoperative Manifest Sphere afN 11/85 1125 12/110

> +1001 (Hyeroic)0.2095 % 12.9% 4.0% 10.9% -> +1.OOD (Hyperopic) ~~~Cl (6.6, 22.0) (0.1, 20.4) (5.8, 18.3)

Postoperative Manifest Sphere nJN 0/85 2/25 2/110< -1.01) (Mopic)0.0088 % 0.0% 8.0% 1.8% -

<-l.00D(Myopic) ~~~ ~~~Cl (0.0, 4.2) (1.0, 26.0) (0.2, 6.4) _ ___

*Cochran-Mvantel-Haenszel (CMHI) Test with rank scores** One-sided exact binomial test comparison to the FDA targetCl = 95% Confidence Interval p < 0.05 is statistically significantUCVA = Uncorrected Visual Acuity MRSE = Manifest Refraction Spherical EquivalentD = Diopter BSCVA = Best Spectacle Corrected Vi~sual Acuity

of 52 7260-0105SRev. A 7



Criteri CMImyopic Hlyperopic Total FDA TargetP-Value ~Defocus Defocus P-Value*"

Key Effectiveness Parametersn/N 56/85 14/25 70/110

UCVA 20/20 or better 0.3687 % 65.9% 56.0% 63.6% -

_________________________ ~Cl 5.,7.) (49 66 (53.9, 72.6)n/N 83/85 25/25 108/I 10 > 5

UCVA 20/40 or better 0.44 10 % 97.6% 100.0% 98.2% .0000_________________________ ~CI (9.,99728.3 0.0 9., 99.8)

n/N 64/85 20/25 84/110 > 0MRSE ± 0.50D 0.6279 % 75.3% 80.0% 76.4% Ž50

_________________________ ~Cl (64.7, 84.0) (59.3, 93.2) (67.3, 83.9) _ ____

n/N 77/85 23/25 100/110MRSE + fOO0D 0.8299 % 90.6% 92.0% 90.9% 10000%

Cl (82.3, 95.8) (74.0, 99.0) (83.9, 95.6) _________

Accuracy of Manifest Sphere and Cs indern/N 59/85 19/25 78/I110

Manifest Sphere ± 0O5OD 0.5257 % 69.4% 76.0% 70.9% -

_________________________ ~Cl (58.5, 79.0) (54.9, 90.6) (61.5,79.2)

n/N 73/85 24/25 97/1 10Manifest Sphere ± 1.OOD3 0.1703 % 85.9% 96.0% 88.2% -

_________________________ ~CI (76.6, 92.5) (79.6, 99.9) (80.6, 93.6)

Manifest Cylinder Magnitude nfN 55/85 16/25 71/110<0.50D 0.9485 % 64.7% 64.0% 64.5% -

_________________________ ~CI 5.,7.) (25 20 (54.9, 73.4)Manifest Cylinder Magnituden/N 78/85 20/25 98/110

M ifet.OOD e Mgitd 0.0987 % 91.8% 80.0% 89.1% -

< ______________D_ ___I _ Cl (83.8, 96.6) (59.3, 93.2) (81.7, 94.2) ______

Postoperative Manifest Spherical Eq uivalent and Manifet Sphere ____ _____

Postoperative MRSE n/N 8/85 0/25 8/110> +1.0D (yperpic)0.1128 % 9.4% 0.0% 7.3% -

> +1.OOD (Hyperopic) ~~~Cl (4.2, 17.7) (0.0, 13.7) (3.2, 13.8)

Postoperative MRSE n/N 0/85 2/25 2/I J0< -1.013 Myop .c)0.0088 % 0.0% 8.0% 1.8% -

<-lOOD (Myopic) ~~~ ~~~CI (0.0, 4.2) (1.0, 26.0) (0.2, 6.4)

Postoperative Manifest Sphere 0.73 n/N 12/85 1/25 13/110> +1.0D (Hperopc) 0.703 % 14.1% 4.0% 11.8%

> +I.OOD (Hyperopic) ~~~Cl 75,34) (.,04 (6.4, 19.4)

Postoperative Manifest Sphere nN 0/85 0/25 0/110< -1.0D (Mopic)NA % 0.0% 0.0% 0.0% -

<-lOOD (Myopic) ~~~~~Cl (0.0, 4.2) (0.0, 13.7) ,(0.0, 3.3) _____

*Cochran-Mantel-Haenszel (CMH) Test with rank scores NA = Not Applicable

** One-sided exact binomial test comparison to the FDA targetCl = 95% Confidence Interval p < 0.05 is statistically significantUCVA = Uncorrected Visual Acuity MRSE = Manifest Refraction Spherical EquivalentO = Diopter BSCVA =Best Spectacle Corrected Visual Acuity

7260.0105 Rev. A of 52 9

CustomnCornea® LASIK Patient Information Booklet - Mixed Astigmatism

AlconLJXEJI/I IXV 10 II'.)S%./' 4

Excimer Laser System

FACTS YOU NEED TO KNOW ABOUTCustomCornea® LASER ASSISTED IN-SITU

KERATOMILEUSIS (LASIK) SURGERY

PATIENT INFORMATION BOOKLET

For Mixed Astigmatism of 11.000) to less than 5.000) cycloplegic cylinder magnitude

Please read this entire booklet. Discuss its contents with your doctor so that youhave all of your questions answered to your satisfaction. Ask any questions youmay have before you agree to the surgery.

Alcon, Inc.2501 Discovery Drive, Suite 500

Orlando, FL 32826 U.S.A.

Tel: (877) 523-2784Fax: (407) '384-1677www.ladarvision.conm

Outside the U.S., contact your local Alcon office

7260-0104 Rev A Page 1 of 29

CustomCornea® LASIK Patient Information Booklet - Mixed Astigmatism

0 2006 Alcon, Inc.

This booklet may be reproduced only by a treating physician for use with patients considering CustomCornea®Laser Assisted In-Situ Keratomileusis (LASIK) Surgery using the LADARVision®4000 System. All other rightsreserved.



A DCN 10065 -original release

Page 2 of 29 7260-0104 Rev A


TABLE OF CONTENTS

A. INTRODUCTION ............................................................................................................ 5

B. How DOES CUSTOMCORNEA® LASIK CORRECT MIXED ASTIGMATISM? ......................... 6

C. BENEFITS OF CUSTOMCORNEA® LASIK ....................................................................... 8CLINICAL STUDY TO EVALUATE BENEFITS ..................................................................... 8

Patient Demographics ........................................................................................... 8Visual Acuity Measurement ................................................................................... 8Visual Acuity without Glasses ................................................................................ 9Visual Acuity without Glasses After Surgery and with Glasses Before Surgery ..... 9Patient Demographics and Surgery Outcomes .................................................... 10Patient Questionnaire .......................................................................................... 10

D. RISKSOFCUSTOMCORNEA®LASIK ........................................................................... 12CONTRAINDICATIONS - WHEN CAN'T You HAVE SURGERY? ........................................ 12

WHAT WARNINGS AND OTHER INFORMATION Do You NEED TO KNOW ABOUT? ............. 1 3

Warnings ............................................................................................................. 13Precautions .......................................................................................................... 13During the First Week Following Surgery ............................................................ 14During One to Six Months Following Surgery ...................................................... 15

CLINICAL STUDY TO EVALUATE RISKS ......................................................................... 15

V isual A cuity w ith G lasses ................................................................................... 15Change in Visual Acuity with Glasses After Surgery ........................................... 16C o ntrast S ensitivity ....................................................... ....................................... 16Adverse Events and Complications ..................................................................... 17Worse and Significantly Worse Symptoms After Surgery .................................... 18

E. ARE YOU A GOOD CANDIDATE FOR CUSTOMCORNEA® LASIK? ................................... 19

F. WHAT SHOULD You EXPECT DURING CUSTOMCORNEA® LASIK SURGERY? ................. 19BEFORE THE SURGERY .............................................................................................. 19

T H E D A Y O F S U RG ERY .............................................................................................. 19

THE FIRST DAYS AFTER SURGERY ............................................................................. 20

G. QUESTIONS TO ASK YOUR DOCTOR ............................................................................ 21

H . S EL F -T E ST ..................... .................................................. 2....................................... 22

I. SUMMARY OF IMPORTANT INFORMATION ..................................................................... 23

J . G L O S S A R Y ............................................................................................................... 2 4

K. PATIENT ASSISTANCE INFORMATION ........................................................................... 27

L . IN D E X .................................... ............... ............................... 2......... ................. 2 8

7260-0104 Rev. A Page 3 of 29



Page 4 of 29 7260-0104 Rev. A

I


A. Introduction

The purpose of this booklet is to provide you with information on laser eye surgery. Please readthis entire booklet carefully. See the "Glossary" (Section J) for an explanation of words shown initalics. Discuss your questions with a doctor trained in laser eye surgery. You need tounderstand the benefits and risks of this surgery before making a decision to have surgery.

Mixed astigmatism is a condition that causes blurred distant and near vision because the eye isboth nearsighted and farsighted. If you have mixed astigmatism, you may have difficulty seeingclearly at distance and near. Glasses, contact lenses, or eye surgery can correct mixedastigmatism to help you see more clearly.

Laser Assisted In-Situ Keratomileusis (LASIK) is a type of eye surgery available to correctmixed astigmatism. Other eye surgeries that may be an option to correct vision are AutomatedLamellar Keratoplasty (ALK) and Radial Keratotomy (RK). These surgeries may not meet thevision requirements for some careers, such as military service.

LASI[K surgery can help you see more clearly by changing the shape of the cornea, the clearfront surface of your eye. LASIK surgery uses an excinier laser to remove tissue to reshape thecornea. An instrument called a microlceratome first cuts a thin flap of tissue from the front ofyour cornea. This corneal flap is folded back, and the laser removes tissue under the flap tochange the shape of the cornea. Then the flap is put back in place for the eye to heal.

Your eyeglass prescription is the usual way to tell how much mixed astigmatism you have.Another way is to measure the shape of the wavefront of reflected light coming out of your eye.A wavefront measurement gives more information about your mixed astigmatism than aneyeglass prescription. A wavefiront measures all of the focusing errors in your eye, includingcomplex errors that eyeglasses cannot correct. These complex focusing errors are called "higher-order abe rrazions

Your doctor can use either your eyeglass prescription or a xvavefront measurement to planLASIK surgery. LASIK surgery based on the eyeglass prescription is called ConventionalLASIK. LASIK surgery based on the wavefiront is called wavefront-guided LASIK.CustomiCornea!) LASIK is wavefront-guided surgery with the LADARVision®4000 ExcimerLaser System.

LASIK surgery is permanent. You can have LASIK surgery on one eye at a time. The secondeye may have surgery on the same day or later, depending upon your choice and your doctor'sadvice. Discuss w\ith your doctor whether you are a good candidate for CustomlCornea®- LASIKsurgery.

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B. How Does CustomCornea® LASIK Correct Mixed Astigmatism?

You see objects because your eye focuses light into images. Your eye works like a camera. Thecamera lens focuses light to form clear images on film. Both the cornea and lens in the eye focuslight on the retina, the back surface of your eye. Diagram 1 shows that distant vision is clearwhen light focuses correctly.

DIAGRAM 1: NORMAL EYECORNEA

RETINA-, Light focuses on the retina.Vision is clear.

A NORMAL EYELENS

Astigmatism is a focusing error that results in blurred distant and near vision. The cornea ismore curved in some directions than others causing light to focus at different points from theretina. Vision is blurred because light does not focus correctly on the retina. When light focusesat a point in front of the retina, the eye is nearsighted. When light focuses at a point behind theretina, the eye is farsighted. An eye with mixed astigmatism is both nearsighted and farsighted.Diagram 2 shows how light focusing at different points from the retina causes blurred vision inan eye with mixed astigmatism.

DIAGRAM 2: EYE WITH MIXED ASTIGMATISM

Light focuses in front of and_%, behind the retina.

A MIXED ASTIGMATIC EYE Vision is blurred.

Wearing glasses and contact lenses help your eye focus light properly on the retina. LASIKsurgery focuses light properly by reshaping the cornea. LASIK surgery uses an excimer laser toremove a tiny amount of tissue from the cornea. This type of laser does not change any otherparts of the eye. Diagram 3 shows that distant vision is clearer after LASIK.

DIAGRAM 3: CORRECTION OF VISION AFTER LASIK

CORNEA

Light focuses on the retina aftersurgery.Vision is clear.

LENS

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CustomCornea ®' LASIK Patient Information Booklet - Mixed Astigmatism

CustomCornea® LASIK uses a wavefront unique to your eye for treatment. This wavefront isused to guide the laser that reshapes the cornea to correct focusing errors. The doctor measuresthe wavefront by projecting light into your eye and measuring the reflected light that comes outof your eye.

The LADARVision®4000 System uses a very small laser beam to reshape the cornea. To correctfor mixed astigmatism, the cornea receives hundreds to thousands of laser pulses during LASIKsurgery. The system must place the laser pulses accurately to precisely reshape the cornea.Precise shaping of the cornea requires tracking and compensating for eye movement duringsurgery.

Your eyes are constantly making small movements. Some of these movements are involuntaryand you do not notice them. You cannot hold your eye perfectly still even if you try. TheLADARVision®4000 System tracks and adjusts for eye movement during surgery. A high-speedactive eye tracking system, called the LADARTracker® system, measures the eye position 4000times a second.

In a clinical study', eye movement during surgery using the LADARVision® System wasevaluated for 554 eyes. This study showed that:

* All eyes moved during surgery.* The LADARTracker® system adjusted for this eye movement. The results of the surgery

were about the same for eyes with large or small eye movements.*. Active eye tracking with the LADARTracker® system improves the accuracy of corneal

shaping.

Without a system to track eye movements, any movement of the eye during surgery could moveit away from its correct position under the laser beam. Before each laser pulse, theLADARTracker® system calculates where the eye has moved since the last pulse and moves thebeam in exactly the same way, so the laser beam hits the cornea in the same place as if the eyehad not moved.

aLADARVision> System PRK Myopia and Astigmatism study

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C. Benefits of CustomCornea® LASIK

CustomCornea® LASIK surgery can correct between 1.00 to less than 5.00 diopters (D) of mixedastigmatism. If you have mixed astigmatism within this range, CustomCornea® LASIK surgerymay help you clearly see distant objects without eyeglasses or contact lenses.

Clinical Study to Evaluate Benefits

A clinical study using the LADARVision®4000 System was done to evaluate the benefits andrisks of CustomCornea® LASIK. The study included 110 eyes to determine benefits and risks.The study results are shown below and in "Risks of CustomCornea® LASIK" (Section D).

Patient Demographics

Table I shows the age, race, gender, and contact lens history of patients in the study.

Table 1. Demographics of 110 Eyes of 63 Study Patients

Age Race Gender Contact LensHistory

Average: 40.6 ± 10.7 years Caucasian 94.5% Female 53.6% None 64.5%Range: 20 to 60 years Hispanic 3.6% Male 46.4% Hard 2.7%

Indian 1.8% Soft 32.7%

Visual Acuity Measurement

Visual acuity is a measure of the sharpness of vision using a letter chart. Diagram 4 shows anexample of a visual acuity chart consisting of lines of letters. Each line of letters becomessmaller from top to bottom on the chart. Vision is sharper as smaller letters are correctly readfrom top to bottom. The chart is read at a distance to measure the sharpness of distant vision.Visual acuity is shown by two numbers: the first number is the distance and the second numberis the smallest line of letters read correctly. As the second number becomes smaller, the vision issharper. For example, a smaller line of letters is read correctly for a visual acuity of 20/20compared to 20/40.

DIAGRAM 4: EXAMPLE OF VISUAL ACUITY CHART

Z V E R DH V D E P

DZ NU VH P E D R

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Visual Acuity without Glasses

The clinical study evaluated visual acuity without glasses at a distance using a letter chart. Table2 shows that at least 93.5% of patients treated for mixed astigmatism saw 20/40 or better withoutglasses after surgery. Most states require that your vision be 20/40 or better if you drive withoutany glasses or contact lenses.

Table 2. Visual Acuity without Glasses

% of Eyes With: Before Surgery I Month 3 Months 6 Months 9 Months(N=110) (N=110) (N=110) ,(N=I10) (N-=108)

20/20 or better* 1.1% 72.3% 63.8% 71.3% 69.6%20/20 or better 0.9% 63.6% 56.4% 63.6% 61.1%20/25 or better 3.6% 86.4% 80.9% 87.3% 84.3%20/40 or better 35.5% 96.4% 95.5% 98.2% 93.5%

* if visual acuity was 20/20 or better with glasses or contact lenses before surgery(N=94 eyes at all visits up to 6 months; N=92 at 9 months). N is the number of eyes studied.

Visual Acuity without Glasses After Surgery and with Glasses Before Surgery

The clinical study compared visual acuity without glasses at a distance after surgery to visualacuity with glasses before surgery using a letter chart. Table 3 shows that 56.4% of patients at3 months and 60.0% at 6 months, saw as well or better without glasses after CustomCornea®surgery as with glasses before surgery.

Table 3. Visual Acuity without Glasses After Surgery Compared towith Glasses Before Surgery

I Month 3 Months 6 Months 9 Months% of Eyes With: (N=110) (N=110) (N=110) (N=108)

2 lines better vision without glasses after LASIKthan vision with glasses before surgery

I line better vision without glasses after LASIK 11.8% 16.4% 17.3% 18.5%than vision with glasses before surgerysame vision* without glasses after LASIK as 48.2% 40.0% 40.9% 39.8%vision with glasses before surgery1 line worse vision without glasses after LASIK 23.6% 19.1% 26.4% 19.4%than vision with glasses before surgery2 lines worse vision wsithout glasses after LASIK 8.2% 11.8% 6.4% 10.2%than vision with glasses before surgerymore than 2 lines worse vision wt]hout glassesafter LASIK than vision with glasses before surgery

* Same vision is within 2 or 3 letters on the same line of a visual acuity chart.N is the number of eves studied.

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Patient Demographics and Surgery Outcomes

Patient demographics were related to the following surgery outcomes in the clinical study at3 months after surgery.

A visual acuity of 20/20 or better without glasses or contact lenses after surgery was morelikely in younger patients and patients with lower amounts of astigmatism before surgery. Avisual acuity of 20/40 or better without glasses or contact lenses after surgery was morelikely in younger patients.

* Reduction of farsightedness or nearsightedness to 0.50D or less after surgery was more likelyin younger patients, Caucasian patients* and patients with low er amounts of astigmatismbefore surgery. Reduction of farsightedness or nearsightedness to I .OOD or less after surgerywas more likely in patients with lower amounts of astigmatism before surgery.

* Reduction of astigmatism to 0.50D) or less after surgery was more likely in patients withlower amounts of astigmatism before surgery. Reduction of astigmatism to I .OOD or lessafter surgery was more likely in females, Caucasian patients* and patients with loweramounts of astigmatism before surgery.

Patient demographics were related to the following surgery outcomes in the clinical study at6 monoths after surgery.

* A visual acuity of 20/20 or better without glasses or contact lenses after surgery was morelikely in patients with lower amounts of astigmatism before surgery.

* Reduction of farsightedness or nearsightedness to 0.50D or less after surgery was more likelyin younger patients, Caucasian patients* and patients with lower amounts of astigmatismbefore surgery. Reduction of farsightedness or nearsightedness to I .00D or less after surgerywas more likely in younger patients and patients with lower amounts of astigmatism beforesurgery.

* Reduction of astigmatism to 1.000) or less after surgery was more likely in females andpatients with lower amounts of astigmatism before surgery.

*Note that the clinical study included only 5.5% of patients of races other than Caucasian.

Patient Questionnaire

Patients in the clinical study were asked to rate the quality of vision after surgery compared totheir recollection of quality of vision before surgery. Table 4 shows that compared to beforesurgery, quality of vision without glasses or contact lenses at 6 months after surgery was reportedas better or significantly better in 86.3% of eyes, same in 4.5% and worse or significantly worsein 9.1%.

Page 1 0of 29 7260-01 04 Rev. A 0


Table 4. Quality of Vision without Glasses or Contact Lenses After SurgeryCompared to Before Surgery*

3 MONTHS 6 MONTHS____________________ N=108 N=1 10

Significantly Better 54.6% 52.7%Better 28.7% 33.6%Same 7A4% 4.5%Worse 7.4% 5.5%Significantly Worse 1.9% 3.6%

N is the number of eyes studied.*Based on the patients' comparison of quality of vision after surgery as better or worse compared totheir recollection of quality of vision before surgery.

Table 5 shows that satisfaction with surgery at 6 months was reported as satisfied or extremelysatisfied in 73i7% of eyes, unsure in 10.9%, and unsatisfied or extremely unsatisfied in 15.4%.

Table 5. Satisfaction with Surgery

3 MONTHS 6 MONTHS_____________________ N=108 N=l1l0

Extremely Satisfied 47.2% 48.2%Satisfied 26.9% 25.5%Not Sure 15.7% 10.9%Unsatisfied 6.5% 11.8%Extremely Unsatisfied 3.7% 3.6%

N is the number of eyes studied.

Table 6 shows that frequency of wearing glasses or contact lenses for distance vision at 6 monthswas reported as never in 8 1.8% of eyes and at least some of the time in 18.2% with frequent orconstant use in 11.8%.

Table 6. Frequency of Glasses or Contact Lens Wear for Distance After Surgery

3 MONTHS 6 MONTHSN=108 N=1 10

Never 85.2% 8 1.8%Seldomn 3.7% 6.4%Frequently 1.9% 1.8%Constantly 9.3% 10.0%


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D. Risks of CustomCornea® LASIK

If you are not satisfied with your surgery results, your doctor may suggest another surgery. Nodata are available for CustomComea® LASIK retreatments.

IMPORTANT: You may need to wear glasses or contact lenses for some activities aftersurgery. CustomCornea® LASIK does not take away the need for reading glasses. You mayneed reading glasses after CustomCornea® LASIK even if you did not need them before.

In some cases, your best vision with glasses or contact lenses may be worse afterCustomCornea® LASIK surgery than it was before surgery.

A number of risks from LASIK surgery are related to the corneal flap rather than the lasertreatment. Some specific problems include: cutting an incomplete or irregular flap, loss of theflap, misalignment of the flap, and cutting all the way through the cornea with themicrokeratome. These problems can lead to other complications, such as infections, cataracts,and permanent scarring or deformity of the eye.

Contraindications - When Can't You Have Surgery?

If you have any of the following situations or conditions, the risk of LASIK surgery is greaterthan the benefit. You should NOT have LASIK surgery if you:

are pregnant or nursing. These conditions may cause temporary and unpredictable changesin your cornea that may interfere with the accuracy of the measurement of your cornea beforethe LASIK procedure.

* have a collagen vascular (e.g., rheumatoid arthritis), autoinimune (e.g., lupus), orimmunodeficiency' disease (e.g., AIDS). These conditions affect your body's ability to healand may result in inflammation or swelling of parts of the body such as muscles, joints, andblood vessels.

* show signs of keratoconus or any other condition that causes a thinning of your cornea. Thisunstable condition of the cornea makes it unsafe to do LASIK procedures on eyes with thiscondition.

* are taking medications with ocular side effects, such as isotretinoin (Accutane 2) for acnetreatment or amiodarone hydrochloride (Cordarone 3) for normalizing heart rhythm. Thesemedications may affect the accuracy of the LASIK procedure or the way your cornea healsafter surgery. This may result in poor vision after surgery.

2Accu/ane Reg. TM of Hoffmann-La Roche Inc.

Cordarone Reg. TM of Sanofi-Aventis

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CustomCornea' LASIK Patient Information Booklet - Mixed Astigmatism

What Warnings and Other Information Do You Need to Know About?

Warnings

If you have any of the following conditions, you may have LASIK if your doctor evaluates theseriousness of your condition and believes the benefit of having LASIK is greater than the risk.Discuss with your doctor if you have:

* diabetes. Diabetes may interfere with the healing of the cornea after LASIK.

* a history of herpes simplex or herpes zoster infection that has affected your eyes. LASIKmay be more risky for patients who have an active or previous herpes infection that hasaffected their eyes.

* significant dry eye that is unresponsive to treatment. LASIK may increase the dry eyecondition, which may or may not go away. This dryness may delay healing of the flap orinterfere with the surface of the eye after surgery.

* severe allergies. The medications taken for severe allergies may interfere with the ability ofthe eye to heal after LASIK.

You will need eye drops to enlarge your pupil to at least 7mm to 11 mm before surgery so thetracking system can more easily follow your eye during surgery. This effect of eye drops is onlytemporary.

Precautions

If you have any of the following conditions, you should discuss this with your doctor. The safetyand effectiveness for LASIK have NOT been established in patients:

* with unstable mixed astigmatism. Eyes with unstable mixed astigmatism are unable to bemeasured correctly to determine the right amount of the vision correction to provide.

• with conditions that may interfere with the ability to properly measure the eye to determinethe right amount of vision correction, and may also affect the healing of the eye after thesurgery, such as:- disease or corneal condition (for example, scar, infection, etc.).- injury to the cornea where LASIK will reshape the cornea.- previous surgery on the cornea or inside the eye (for example, cataract surgery).- prior history of surgery to correct vision (for example, LASIK surgery).

* with a cornea that is too thin for LASIK to be completed safely. A flap needs to be cut intothe cornea for the LASIK procedure. A proper flap cannot be created on a thin cornea.

* with a history of glaucoma (a condition usually associated with high eye pressure withdamage to the nerve in the eye and possible loss of vision). It is unknown whether LASIK issafe for eyes with glaucoma.

7260-0104 Rev. A Page 13 of 29


* who are taking the medication sumatripin succinate (Imitrex 4) for migraine headaches. It isunknown whether the use of this medication will interfere with the accuracy of themeasurement of your cornea prior to LASIK or the healing of the eye after LASIK.

* under 21 years of age because it is unknown if the eye has reached its adult vision refraction.This may result in measurement of the amount of correction to provide being incorrect.

* over the long term (more than 9 months).

* with mixed astigmatism less than 1.00D or for 5.00D or greater. Corrections falling outsideof the approved range have not been studied.

* for retreatment with this laser for LASIK. Retreatments have not-been done enough times toallow an understanding of whether it is safe and effective.

Let your doctor know if you are taking any prescription medicines or any medications youbought without a prescription. These medications may interfere with the measurement prior toLASIK or the healing of the eye after LASIK.

The safety and effectiveness of wavefront-guided LASIK have only been established with anoptical zone of 6.5mm and a total treatment zone of 9.0mm.

Before surgery, your doctor should evaluate your pupil size under dim lighting conditions. Ifyour pupils in dim light are greater than the optical zone (> 6.5mm) proposed by your doctor,consult with your doctor about the risk that the surgery may cause negative effects on yourvision, such as glare, halos, and night driving difficulty.

Your doctor should also evaluate you for dry eyes before surgery. You may have dry eyes afterLASIK surgery even if you did not have dry eyes before surgery.

During the First Week Following Surgery

* You may feel pain, discomfort, or have a feeling that something is in your eye. It may last upto 7 days after surgery.

* Your vision may be blurry or you may become more sensitive to light as your eye heals.

* You may have temporary swelling of the front surface of your eye.

* The pressure inside your eye may increase, usually due to the use of anti-inflammatorymedication (eye drops) after surgery. Using another medication or stopping the anti-inflammatory medication can control the abnormal increase in eye pressure.

4hnioex Reg TM of Glaxo Group Limited

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During One to Six Months Following Surgery

* Your vision should be stable 3 months after surgery. Some patients may notice that theirvision improves or worsens. These small changes may occur up to 6 months or more aftersurgery. You should contact your doctor if you notice any change or loss of vision.

* You may become more sensitive to light. You may notice glare or have difficulty in drivingat night.

* You may experience some dryness.

Clinical Study to Evaluate Risks

In the clinical study using the LADARVision®4000 System for CustomCornea® LASIK, somepeople still needed glasses or contact lenses after surgery.

Astigmatism remained after surgery for some patients. After surgery, 9.1% of patients at3 months and 10.9% of patients at 6 months had astigmatism of more than ID and 0.9% ofpatients at 3 and 6 months had astigmatism of more than 2D.

Farsightedness remained after surgery for some patients. After surgery, 5.5% of patients at3 months and 7.3% of patients at 6 months had more than ID of farsightedness and 0.9% ofpatients at 3 months had more than 2D of farsightedness. Older patients, primarily between 40and 60 years, were more likely to have more than ID of farsightedness at 3 and 6 months.Patients with higher amounts of astigmatism before surgery were more likely to have ID offarsightedness at 3 months after surgery.

Nearsightedness remained after surgery for some patients. At 3 and 6 months, 1.8% of patientshad more than ID of nearsightedness. Younger patients were more likely to have more than IDof nearsightedness at 3 and 6 months, which was observed in both eyes of a 20 year-old patient.

Visual Acuity with Glasses

The clinical study evaluated visual acuity with glasses at a distance using a letter chart. Table 7shows that all patients in the study saw 20/25 or better with glasses before surgery and at 3months or later after surgery.

Table 7. Visual Acuity wiit Glasses (Best Vision)

% of Eyes With: Before Surgery 1 Month 3 Months 6 Months 9 Months______ (N=110) (N=110) (N--110) _4=110_(N=108)

20/20 or better 85.5% 89.1% 89.1% 92.7% 93.5%20/25 or better 100.0% 99.1% 100.0% 100.0% 100.0%20/32 or better 100.0% 100.0% 100.0% 100.0% 100.0%


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Change in Visual Acuity with Glasses After Surgery

Under dim room lighting conditions, the change in best vision with glasses after surgery wascompared to vision with glasses before surgery using a standard (high-contrast) visual acuitychart and a 10% low contrast visual acuity chart. A standard chart has black letters on a whitebackground. A 10% low contrast visual acuity chart has gray letters on a white background.Black letters are easier to see than gray letters. Low contrast visual acuity testing is a way todetermine how well patients can see in poor contrast conditions such as very dim light, rain,snow, and fog. Table 8 compares the change in vision with glasses before surgery to 3 and 6months after surgery.

Table 8. Change in Visual Acuity with Glasses After SurgeryCompared to Before Surgery

Standard Chart 10% Low Contrast Chart% of Eyes With: 3 Months 6 Months 3 Months 6 Months

(N-I10) (N=1 10) (N=108) (N=110)

loss of more than 2 lines 0.0% 0.0% 0.9% 0.0%

loss of 2 lines 0.0% 0.0% 3.7% 2.7%

loss of I line 6.4% 3.6% 17.6% 19.1%

no change 53.6% 54.5% 39.8% 36.4%

gain of I line 39.1% 38.2% 30.6% 33.6%gain of 2 lines 0.9% 3.6% 6.5% 7.3%

gain of more than 2 lines 0.0% 0.0% 0.9% 0.9%N is the number of eyes studied.

Contrast Sensitivity

In the clinical study, contrast sensitivity was measured in daylight and in dim light to determinehow well patients can see in poor contrast conditions such as very dim light, rain, snow, and fog.The majority of subjects reported no change before and after surgery. Table 9 compares thechange in contrast sensitivity with glasses before surgery to 3 and 6 months after surgery.

Table 9. Change in Contrast Sensitivity with Glasses After SurgeryCompared to Before Surgery

Daylight Conditions Dim Light Conditions% of Eyes With: 3 Months 6 Months 3 Months 6 Months

( =110) (N=110) (N=107) (N-107)Loss 6.4% 5.5% 11.2% 10.3%No change 90.9% 89.1% 66.4% 63.6%

Gain ] 2.7% J 5.5% 22.4% 26.2%N is the number of eyes studied.

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Adverse Events and Complications

Some patients from the clinical study experienced adverse events and complications afterCustomCornea® LASIK surgery as shown in Table 10.

Table 10. Adverse Events and Complications

Greater than or equal to 1% of eyes (N=I 10) had:Irritation on the front surface of the cornea at one month or later 10.0%Cells growing under the corneal flap *.5.4%

Inflammation of the cornea under the corneal flap 4.5%Problem with creation of the cornea! flap *1.8%

Pain at one month or later 1.8%

Less than 1% of eyes (N=1 10) had:Feeling of something in the eye at one month or later 0.9%Viral infection in the cornea J 0.9%

N is the number of eyes studied.*One eye did not receive laser ablation after a problem with the creation of the corneal flapand was not included in the analysis of eyes receiving laser surgery (N1l II1).


* blockage of blood vessels in the retina;

* breakdown of the flap;

* corneal swelling;

* cells growing under the corneal flap with a loss of 2 or more lines of visual acuity withglasses;

* corneal scratch involving the treated area or outside the treated area at one month or later;* corneal cloudiness at six months or later with a loss of 2 or more lines of visual acuity with

glasses;

* eye pressure more than 25 mrmffg;

*increase in eye pressure of more than I0 mmHg compared to before surgery;

* loss of more than 10 letters (more than 2 lines) of visual acuity with glasses at six monthsor later;

* poor alignment of the corneal flap~ and

* separation of the retina from the back of the eve.

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Worse and Significantly Worse Symptoms After Surgery

Patients who were treated for mixed astigmatism in the clinical study rated the change in thefollowing symptoms shown in Table I 1 as worse or significantly worse after surgery withoutglasses or contact lenses compared to their recollection of symptoms before surgery. Thesymptoms reported as "worse" or "significantly worse" in >10% of eyes at 6 months weredryness, light sensitivity, blurring of vision, fluctuation of vision, glare, halos, and night drivingdifficulty.

Table 11. Worse or Significantly Worse Symptoms without Glasses After SurgeryCompared to Before Surgery*

3 Months (N=1 10) 6 Months (N=1 10)

Comfort Symptoms Worse Significantly Worse SignificantlyWorse Worse

Burning 2.7% 0.9% 6.4% 0.9%Dryness 40.0% 1.8% 36.4% 2.7%Excessive Tearing 0.0% 0.0% 2.7% 0.0%Gritty Feeling 6.4% 0.9% 6.4% 0.9%Headache 4.5% 0.0% 4.5% 0.0%Light Sensitivity 27.3% 0.0% 20.9% 1.8%Pain 6.4% 1.8% 4.5% 0.0%Redness 4.5% 1.8% 7.3% 0.0%Visual SymptomsBlurring of Vision 20.0% 1.8% 13.6% 8.2%Double Vision 8.2% 0.0% 4.5% 1.8%Fluctuation of Vision 20.0% 3.6% 21.8% 4.5%Glare 26.4% 0.0% 13.6% 0.0%Halos § 27.3% 0.0% 19.1% 3.6%Night Driving Difficulty 20.0% 0.0% 10.9% 3.6%

N is the number of eyes studied.* Based on the patients' comparison of symptom severity after surgery as worse compared to their

recollection of symptom severity before surgery.§ Halos are circular flares or rings of light that may appear around a headlight or other lighted object.

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E. Are You a Good Candidate For CustomCornea® LASIK?

If you are considering CustomCornea® LASIK, you must:

* be at least 21 years of age.* have a healthy eye with no eye disease or comeal condition (for example, scar or infection).* have mixed astigmatism of 1.00D to less than 5.OOD.* have stable mixed astigmatism as documented by less than or equal to 0.50D change each

year for at least one year before your eye examination before surgery.• be able to lie flat on your back.* be able to look at a blinking fixation light during the entire surgery.* be able to have eye drops that numb your eye and enlarge your pupil.* understand the risks and benefits of CustomCornea® LASIK compared to other available

treatments for mixed astigmatism.* be willing to sign an Informed Consent Form, if provided by your doctor.

F. What Should You Expect During CustomCornea® LASIK Surgery?

Before the Surgery

Before surgery, your doctor needs to determine your complete medical and eye history and checkthe health of both your eyes. As part of this exam, your doctor will use a computer program tomap the front surface of your eye. This exam will determine if your eyes are healthy and if youare a good candidate for CustomCornea® LASIK.

WARNING: You must stop wearing any contact lenses at least 3 weeks before this eyeexamination. Failure to do this may affect surgical results.

Tell your doctor if you take any prescription and non-prescription medications or have anyallergies. Ask your doctor if you should eat or drink right before the surgery. You should alsoarrange for transportation since you must not drive right after the surgery. Your doctorwill let you know when your vision is good enough to drive again.

The Day of Surgery

To prepare for surgery, your doctor will use the wavefront system to take a picture of your eye.This helps to determine where the laser should treat your cornea. Your doctor will put eye dropsto dilate (enlarge) the pupil in your eye(s). After 30-40 minutes, your doctor will measure thewavefront unique to your eye to determine the amount of laser treatment you need.

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CustomCornea ® LASIK Patient Information Booklet - Mixed Astigmatism

Your doctor will then place numbing eye drops in the eye to be treated. Numbing drops are usedto control pain during surgery. The effects of the numbing eye drops will wear off after about45-60 minutes. Your doctor will ask you to lie on your back on the laser bed. The laser bed is aflat cushioned surface that can be moved to position you for surgery. Your doctor will instructyou to watch a blinking fixation light. Your doctor will place an instrument between youreyelids to hold them open during the surgery. A temporary shield will cover the eye that is nothaving surgery.

An instrument called the microkeratome creates a flap of tissue in the cornea. Then, your doctorwill reposition your head and activate the LADARTracker® system to track your eye movement.Your doctor will ask you to look directly at the blinking light. The laser in theLADARVision®4000 System will remove small amounts of tissue from your cornea. During thelaser treatment, you will hear a "clicking" sound of laser pulses. The tracking system will followeye movements and allow the laser to continue the treatment. You will be under the laser forseveral minutes. The use of the laser will take about one minute. Overall, the surgery takesabout 10 minutes.

IMPORTANT: You must continue looking at the blinking light throughout the treatment, evenif your vision begins to become cloudy during the procedure.

After the surgery is complete, your doctor will place some eye drops in your eye. Your doctormay cover your eye with a bandage contact lens to help heal the eye. For your eye protectionand comfort, your doctor may apply a patch or shield over your eye.

The First Days After Surgery

You may be mildly sensitive to light and have a feeling that something is in your eye.Sunglasses may make you more comfortable. Also, you may experience pain. Your doctor canprescribe pain medication to make you more comfortable during the first few days after thesurgery. A plastic shield may be used to protect your eye after LASIK. You will need to uselubricants, antibiotic, and anti-inflammatory medications in the first few days.

IMPORTANT: Use the lubricants and eye medications as directed by your doctor. Your resultsdepend upon you following your doctor's instructions.

WARNING: Your doctor will monitor you for any side effects if you need to use a topicalsteroid medication. Possible side effects of prolonged topical steroid use are:* ocular hypertension (an increase in the eye pressure);* glaucoma (a condition usually associated with high eye pressure that results in damage to the

nerve in the eye and possible loss of vision);* cataract formation (an opacity or clouding of the lens inside the eye that can cause a loss of

vision).

DO NOT rub your eyes for the first 3 to 5 days. Rubbing your eye may move the flap. If younotice any sudden decrease in your vision, you should contact your doctor immediately. Theflap may have moved and the doctor may need to reposition the flap.

Page 20 of 29 7260-0104 Rev A

1lS


G. Questions to Ask Your Doctor

You may want to ask the following questions to help you decide if CustomCornea® LASIK withthe LADARVision®4000 System is right for you:

* What are my other options to correct my mixed astigmatism?

* Will I have to limit my activities after surgery and for how long?

* What are the benefits of CustomCornea® LASIK for my amount of mixed astigmatism?

• What vision can I expect in the first few months after surgery?

· If CustomCornea® LASIK does not correct my vision, what is the possibility that my glasseswould need to be stronger than before? Could my need for glasses increase over time?

* Will I be able to wear contact lenses after LASIK if I need them?

* How is LASIK likely to affect my need to wear glasses or contact lenses as I get older?

* Will my cornea heal differently if injured after having LASIK?

* Should I have LASIK surgery in my other eye?

* How long will I have to wait before I can have surgery on my other eye?

* What vision problems might I experience if I have LASIK only on one eye?

* Do I have significant dry eye or large pupils that could produce undesirable side effects afterLASIK surgery?

Discuss the cost of surgery and follow-up care needs with your doctor. Most health insurancepolicies do not cover laser vision correction.

7260-0104 Rev. A Page 21 of29


H. Self-Test

Are You An Informed And Educated Patient?

Take the test below to see if you can correctly answer the following questions after reading thisbooklet.

TRUE FALSE

1. LASIK surgery is risk-free. El F]

2. It does not matter if I wear my contact lenses before surgerywhen my doctor told me not to wear them. [ [

3. Since the LADARVision®4000 System tracks my eyemovements, I do not have to fixate on the blinking light. H E]

4. After the surgery, there is a good chance that I will be lessdependent on eyeglasses or contact lenses. H H

5. I may need reading glasses after LASIK surgery, even if I didnot need them before. F] E]

6. There is a risk that I may lose some vision after LASIK surgery. H H7. It does not matter if I am pregnant. F] H8. If I have an autoimmune disease, I am still a good candidate for

LASIK surgery. F] [

9. Significant dry eye or large pupils may produce undesirable sideeffects after LASIK surgery.

You can find the answers to Self-Test at the bottom of the next page.

Page 22 of 29 7260-0104 Rev. A

117


I. Summary of Important Information

* CustomCornea ® LASIK is a permanent irreversible surgery to the comea.

* You may need to wear glasses or contact lenses for some activities after surgery.CustomCornea® LASIK does not take away the need for reading glasses, even if you havenever worn them before.

* Your vision must be stable before CustomCornea® LASIK surgery. You must providewritten evidence that your mixed astigmatism has changed less than or equal to 0.50D eachyear for at least I year.

* Pregnant and nursing women should wait until they are not pregnant and not nursing to haveCustomCornea® LASIK surgery.

* You would not be a good candidate if you have autoimmune or collagen vascular diseases.If you have a condition that makes wound healing difficult, you would not be a goodcandidate.

* CustomCornea® LASIK surgery has some risks. Please read and understand this entirebooklet, especially the sections on Benefits and Risks before you agree to the surgery.

* Some other options to correct mixed astigmatism include glasses, contact lenses, andConventional LASIK. Other surgical options that may be used to correct vision are ALK andRK.

* ALK, RK and LASIK surgery may not meet the vision requirements of some occupations,such as military service.

* Before considering CustomCornea® LASIK surgery you should:

a. have a complete eye examination.

b. talk with at least one eye care professional about CustomCornea® LASIK, especially thepotential benefits, risks, and complications. You should discuss the time needed forhealing after CustomCornea® LASIK.

Answers to Self-Test Questions:

1. False (see Section D: Risks) 6. True (see Section D: Risks)2. False (see Section F: Before the Surgery) 7. False (see Section D: Contraindications)3. False (see Section F: The Day of Surgery) 8. False (see Section D: Contraindications)4. True (see Section C: Benefits) 9. True (see Section D: Precautions)5. True (see Section D: Risks)

7260-0104 Rev. A Page 23 of 29

'IsI


J. Glossary

This section summarizes important terms used in this information booklet. Please discuss anyrelated questions with your doctor.

Aberration: focusing errors in the eye detectable by wavefront measurements. Examples aremixed astigmatism (lower-order) and complex errors (higher-order).

Antibiotic Medication: a drug used to treat or prevent infection. Your doctor may prescribe thismedication after LASIK surgery.

Anti-inflammatory Medication: a drug that reduces inflammation or the body's reaction toinjury or disease. Any eye surgery can cause inflammation. Your doctor may prescribe thismedication after LASIK surgery.

Astigmatism: a focusing error that results in blurred distant and near vision. The cornea ismore curved in some directions than others causing light to focus at different points from theretina. Vision is blurred because light does not focus correctly on the retina. Types ofastigmatism include nearsighted, farsighted and mixed.

Autoimmune Disease: a condition in which the body attacks itself and results in inflammationor swelling of parts of the body, such as muscles, joints, and blood vessels. An example is lupus.If you have this type of condition, you should not have LASIK surgery.

Automated Lamellar Keratoplasty (ALK): a type of eye surgery that changes the shape of thefront surface of the eye using a microkeratome. A flap is created and tissue is removed under theflap with the microkeratome. Then the flap is put back on the eye.

Bandage Contact Lens: a soft contact lens placed on the cornea after surgery to cover the areathat was treated with the laser.

Cataract: an opacity, or clouding, of the lens inside the eye that can blur vision.

Collagen Vascular Disease: a condition that may result in inflammation or swelling of parts ofthe body, such as muscles, joints, and blood vessels. An example is rheumatoid arthritis. If youhave this type of condition, you should not have LASIK surgery.

Contraindications: any special condition that results in the treatment not being recommended.

Contrast Sensitivity: a measure of the ability of the eye to detect small lightness differencesbetween objects and the background in daylight and in dim light. For example, black lines on agray background are easier to see than gray lines on a gray background. Objects in daylight arealso easier to see than in dim light. Contrast sensitivity testing is a way to determine how wellpatients can see in poor contrast conditions such as very dim light, rain, snow, and fog.

Conventional LASIK: LASIK surgery that uses an eyeglass prescription to plan the surgery.

Cornea: the clear front layer of the eye. LASIK surgery reshapes the front surface of the corneato improve distant vision.

Corneal Flap: a thin slice of tissue on the surface of the cornea made with a mlicrokeratome atthe beginning of the LASIK procedure. This flap is folded back before the laser shapes the innerlayers of the cornea.

Page 24 of 29 7260-0104 Rev. A


Corneal Swelling: abnormal fluid build-up in the cornea. This condition is usually temporarywith no significant effect on vision.

CustomCornea® LASIK: LASIK surgery that uses the wavefront to plan the surgery with theLADARVision®4000 System.

Diopter: a unit of focusing power, used to describe the amount of mixed astigmatism,farsightedness or nearsightedness in an eye. Abbreviated as "D".

Excimer Laser: a form of light energy used in Conventional and CustomCornea® LASIK toremove tissue from the cornea.

Farsightedness: a focusing error that results in blurred vision that is usually worse at near thanat distance. The cornea and lens focus light at a point behind the retina resulting in blurredimages. Farsightedness is also called hyperopia.

Focusing Error: a condition in which the eye forms a blurred image on the retina. Examples aremixed astigmatism, farsightedness, nearsightedness and higher-order aberrations (complexfocusing errors).

Glaucoma: an eye disease usually associated with high eye pressure. Glaucoma damages theoptic nerve of the eye and usually causes a progressive loss of vision.

Halos: circular flares or rings of light that may appear around a headlight or other lighted object.This symptom may occur before or after surgery.

Herpes Simplex: a type of viral infection that can recur. This virus typically causes cold soresand/or vesicles to appear on the face or other parts of the body. You should discuss any historyof this condition with your doctor before having LASIK surgery.

Herpes Zoster: a type of viral infection that can recur. This condition is a reactivation of thechicken pox virus as an adult. Vesicles appear on only one side of the body. You should discussany history of this condition with your doctor before having LASIK surgery.

Immunodeficiency Disease: a condition that compromises the body's ability to heal. Anexample is acquired immunodeficiency syndrome (AIDS). If you have this type of condition,you should not have LASIK surgery.

Inflammation: the body's reaction to injury or disease. Eye surgery can also causeinflammation.

Keratoconus: a condition of the cornea that results in a change in the shape of the cornea withthinning. If you have this condition, you should not have LASIK surgery.

Laser Assisted In-Situ Keratomileusis (LASIK): a type of eye surgery that uses amicrokeratome and a laser to improve vision. The microkeratome creates a thin, hinged flap oftissue on the cornea that is folded back. The laser shapes the tissue under the flap and the flap isput back on the eye so the tissue heals.

Lens: a structure inside the eve that helps to focus light onto the back surface (retina) of the eye.

7260-0104 Rev. A Page 25 of 29


Low Contrast Visual Acuity: a measure of the sharpness of vision using a 10% low contrastchart with gray letters on a white background. Low contrast acuity testing is another way todetermine how well patients can see in poor contrast conditions such as very dim light, rain,snow, and fog.

Microkeratome: a surgical instrument used in LASIK to cut a thin flap of tissue from the frontsurface of the eye before the laser treatment is applied.

Mixed Astigmatism: a focusing error that results in blurred distant and near vision. An eye withmixed astigmatism is both nearsighted and farsighted. The cornea is more curved in somedirections than others causing light to focus at different points in front of and behind the retina.Vision is blurred because light does not focus correctly on the retina. ·

Nearsightedness: a focusing error that results in blurred vision that is usually worse at distancethan at near. The cornea and lens focus light at a point in front of the retina resulting in blurredimages. Nearsightedness is also called myopia.

Ocular Hypertension: increased eye pressure.

Radial Keratotomy (RK): a type of surgery that changes the shape of the front surface of theeye by creating cuts with a blade.

Retina: the layer of nerve tissue at the back of the eye that captures images, similar to film in acamera, and sends information about those images to the brain. Light must be focused correctlyon the retina to form clear images.

Steroid Medication: a drug that reduces inflammation or the body's reaction to injury ordisease. Your doctor may prescribe this medication after LASIK surgery for a short time tomodify the healing of your eye. If you are taking this medication for a disease condition, youshould not have LASIK surgery.

Visual Acuity: a measure of the sharpness of vision using a letter chart.

Wavefront: a measure of the total focusing errors (aberrations) including mixed astigmatism,and complex focusing errors (higher-order aberrations). Light is projected into your eye andfocused on the retina. Part of this light is reflected back out of your eye to form the wavefront.

Page 26 of 29 7260-0104 Rev. A

lb/f


K. Patient Assistance Information

To be completed by you or your Primary Eye Care Professional as a reference.

Primary Eye Care Professional

N am e: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

A ddress: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

Phone:

CustomCornea® LASIK Doctor

Name:

A ddress: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

Phone: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

Treatment Location

Name:

Address:

Phone: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

Laser Manufacturer

Alcon, Inc.2501 Discovery Drive, Suite 500Orlando, FL 32826Tel: (877) 523-2784 Fax: (407) 384-1677

7260-0104 Rev. A Page 27 of 29


L. Index

A DAberration ·6, See also Focusing Error Diabetes. 14

Definition ·25 Diopter. 9Adverse Events - 18 Definition. 26Allergies ·14 Driving 10Astigmatism ·7, See also Mixed Astigmatism After Surgery ·20

Definition ·25 Dry Eye ·14, 15, 22, 23Autoimmune Disease · 13, 23, 24 Dryness 16, 19

Definition 25Automated Lamellar Keratoplasty (ALK) 6 6

Definition ·25 E

Excimer Laser ·6, 7B Definition. 26

Eye Tracking 8, 21Burning ·19 Eyeglass Prescription ·6

C FCataract ·13, 21 Farsightedness ·7

Definition -25 Definition ·26Collagen Vascular Disease 13, 24 Feeling of Something in the Eye · 15, 18, 21

Definition 25 Focusing Error' 6, 7, See also AberrationComplications- 18 Definition ·26Contact Lenses

Bandage ·21, 25Discontinue Wear before Surgery -20 G

Contraindications' 13Definition 25 Glare 15, 16, 19

Contrast Sensitivity · 17 Glaucoma- 14,21Definition -25 Definition. 26

Conventional LASIK -6 Gritty Feeling 19Definition ·25

Cornea · 6, 7Definition ·25 HFlap -6, 13, 18, 21, 26Infection ·13, 18 Halos- 15, 19Scratch -18 Definition ·26Swelling 15, 18, 26 Headache. 19

CustomCornea® LASIK 6 Herpes Simplex6 14Are You A Good Candidate · 20 Definition 26lferpes Zoster- 14Clinical Studies 9. 10, 16, 17, 18 Definition 26Definition -26Hlow Does It Correct Mixed Astigmatism, 7Questions To Ask Your Doctor -22Self-Test - 23Summary oflImportant information -24 Immunodeficiency Disease 13What Are The Benefits- 9 Definition 26What Are the Risks- 13 Inflammation -IWhat To Expect During Surgery 20 Definition 26

Irregular flap · 13

KKeratoconus - 13

Definition ·26

Page 28 of 29 7260-0104 Rev. A


L PLADARTracker® System - 8,21 Pain215,19,21

Precautions.- 14LADARVision®4000 System · 6, 8 Pregnancy t 13, 23, 24

Clinical Studies ·9, 10, 16, 17, 18Tracking Eye Movements 8, 21, 23

Laser Assisted In-Situ Keratomileusis (LASIK) ·6 RDefinition ·27

Lens ·7 Radial Keratotomy (RK) ·6Definition - 27 Definition ·27

Light Sensitivity · 15, 16, 19, 21 Reading Glasses 13,24Redness- 19Retina ·7, 18

M Definition ·27

MedicationAmiodarone Hydrochloride. 13 TAntibiotic ·21, 25Anti-inflammatory ·15, 21, 25 Tearing · 19Isotretinoin. 13Steroid ·21, 27Sumatripin Succinate 15 V

Microkeratome ·6, 21Definition ·27 Vision

Mixed Astigmatism ·6, 7 Blurring 15, 19Definition 27 Double 18, 19

Fluctuation. 16, 19Vision with Glasses. 10, 13, 16, 17, 18

N Vision without Glasses· 10Visual Acuity. 10, 16, 17

Nearsightedness ·7 Definition ·27Definition ·27 Low Contrast 17, 27

Night Driving Difficulty. 15, 16, 19 Measurement 9

O WOcular Hypertension. 18, 21 Warnings. 14

Definition · 27 Wavefront 6Definition ·27

7260-0104 Rev A Page 29 of 29

12L/

CustomnCornea® LASIK Physician's Booklet - Mixed Astigmatism

AlconL =ADEA R6000

E XC I MER L ASE9R

PROFESSIONAL USE INFORMATION MANUAL

FOR CustomnCornea® LASER ASSISTED IN-SITU KERATOMILEUSIS(LASIK)

PHYSICIAN'S BOOKLET

For Mixed Astigmatism of 1.000 to less than 5.OOD cycloplegic cylinder magnitude

RESTRICTED DEVICE: U.S. Federal Law restricts this device to sale, distribution, and use byor on the order of a physician or other licensed eye care practitioner. U.S. Federal Law restrict sthe use of this device to practitioners who have been trained in its calibration and operation, andwho have experience in the surgical management and treatment of refractive errors.

This document provides information concerning the intended clinical use of the LADAR6000OTExcimer Laser System. For complete information concerning system components, safetyinstructions, installation, maintenance, and troubleshooting refer to the LADAR6000T m ExcimerLaser System Operation Manual.

Carefully read all instructions prior to use. Observe all contraindications, warnings, andprecautions noted in these instructions. Failure to do so may result in patient and/or usercomplications.


Orlando, FL 32826

Tel: (877) 523-2784Fax: (407) 384-1677

Outside the U.S., contact your local Alcon representative

7260-0107 Rev. A Page 1 of 52


C 2006 Alcon, Inc.

All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means,electronic or mechanical, including photocopying, recording, or any information storage and retrieval system,without permission in writing from Alcon, Inc.



A DCN 10064 - original release

Page 2 of 52 7260-0107 Rev A


TABLE OF CONTENTS

1. GENERAL SAFETY CONSIDERATIONS ............................................................................... 52. DEVICE DESCRIPTION ......................................................................................................... 5

A. WAVEFRONT MEASUREMENT DEVICE (WMD) ........................................................ . 5B. MICROKERATOME ................................................................................................. 6

C. CUSTOMCORNEA® SURGERY PLANNING SOFTWARE .............................................. . 7D. LADAR6000 EXCIMER LASER SYSTEM ............................................................... 7

3. INDICATIONS, CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, ADVERSEEVENTS AND COMPLICATIONS ........................................................................................ 12A. INDICATIONS FOR USE ........................................................................................ 12B. CONTRAINDICATIONS .......................................................................................... 12C. WARNINGS ......................................................................................................... 12D. PRECAUTIONS .................................................................................................... 13E. ADVERSE EVENTS AND COMPLICATIONS . .............................................................. 14

4. CLINICAL STUDY ................................................................................................................. 15A. INTRODUCTION ................................................................................................... 15B . R E S U LT S ........................................................................................................... 1 7

1 . D e m o g ra p h ics ............................................................................................ 172 . A cco u n ta b ility ............................................................................................. 173. Preoperative Cycloplegic Refraction Parameters ...................................... 184. Key Effectiveness Outcomes ..................................................................... 195. Stability of M anifest R efraction .................................................................. 296. Wavefront Outcomes ......................................... 317. K ey S afety O utcom es ................................................................................ 348. C hange in C ontrast Sensitivity ................................................................... 389. Patient Q uestionnaire ................................................................... 3910. R etreatm ent Qeton40................................................................................3911. Statistical Analysis Outcomes .................................................................... 4112. Comparative Analysis by Defocus Type ................................... 43

C . TRACKING EFFECTIVENESS ................................................................................. 465. PLANNING AND PROCEDURES ..... ....................................... 47

A . PA TIEN T S ELECTIO N 7.... ................................................................................... 4 7

B . O PERAT IVE PRO CEDURE ................................................................................ 48

1. C entration and R egistration ..................................................... ................. 492 . P u p il D ila tio n .............................................................................................. 4 93 . L ase r C a lib ratio n ..... ....... ...................................... ...... ............................. 5 04 . A b la tio n .i................................................................................... ... ........... 5 i

C. POSTOPERATIVE PROCEDURE ........... .................................................. 52

726040107 Rev A Page 3 of 52

t2]



Page4of52 7260-0107 Rev A12-g


1. GENERAL SAFETY CONSIDERATIONS

"WARNING:" - Identifies conditions or practices that could result in damage to equipment orother property, personal injury, or loss of life.

WARNING: Specific training from Alcon or an authorized representative of Alcon is requiredbefore anyone is qualified to operate the LADAR6000T System. Read and understand thismanual and the LADAR6000 Excimer Laser System Operation Manual prior to operating thesystem.

Refer to the LADAR6000 Tm Excimer Laser System Operation Manual for additional warningsregarding use of the LADAR6000 TM System.

2. DEVICE DESCRIPTION

A. WA VEFRONT MEASUREMENT DEVICE (WMD)

The first step in performing CustomCornea® LASIK surgery is to perform a wavefrontexamination on the patient using a wavefront measurement device (WMD) compatible with theLADAR6000 Tm Excimer Laser System. At the present time, the only compatible WMD is theAlcon LADARWave® CustomCornea® Wavefront System.

The LADAR Wave® CustomCornea® Wavefront System is indicated for measuring, recording,and analyzing visual aberrations (such as myopia, hyperopia, astigmatism, coma and sphericalaberration) and for displaying refractive error maps of the eye to assist in prescribing refractivecorrections. This device is enabled to export wavefront data and associated anatomicalregistration information to a compatible treatment laser with an indication for wavefront-guidedrefractive surgery.

Essential features of the compatible WMD are as follows:

Patient Fixation and Fogging

The WMD includes a fixation optical subsystem that provides the patient with an unambiguousfixation point. In addition, the fixation subsystem includes adjustable optics to compensate forthe patient's inherent refractive error. The optics are used to "fog" the eye, first clarifying thefixation target and then it optically adjusts beyond the patient's far point to minimizeaccommodation.

Central ion

Prior to dilation, the WMD is used to record the geometric relationship between the naturaldaytime pupil center and the limbus of the eye. This information is then used to center thewavefront measurement and subsequent ablative treatment on the natural line of sight.

7260-0107 Rev. A PageS5 of 52


Wavefront Measurement

The WMD measures the wavefront profile of the eye with a high degree of accuracy andcharacterizes the profile using Zernike polynomials. The pupil must be large enough so thatvalid wavefront data can be obtained over a large area. Higher-order aberrations are moresignificant at night when the pupil is naturally larger. Therefore, when treating these aberrations,measurement over a large pupil provides the greatest utility.

Registration

The WMD uses synchronized video imagery and on-screen software reticules to record therelationship of the wavefront data to the limbus of the eye and to ink marks applied to the sclerajust before the wavefront exam. This registration information is used to position the excimerablation profile at the correct comeal location and cyclotorsional angle.

Data Export

The WMD has the ability to export the wavefront examination data as an electronic file toremovable media for transfer to the LADAR6000 TM System. The electronic file is structured in aspecific format and contains essential patient information, centration/registration information,and the detailed aberration data. In addition, the electronic file is encrypted in a manner that canonly be deciphered by the LADAR6000 TM System.

B. MICROKERA TOME

A microkeratome is used to achieve a partial thickness cut of the cornea, which creates a "flap"as part of the LASIK procedure. The microkeratome is a precision instrument used in performinglamellar corneal resections. This instrument cuts a precise corneal disc of pre-selected thicknessand diameter. The system generally consists of a head, plates, ring, handle, wrenches, shaft,motor, hand-piece, disposable blades, and power supply with footswitches and power cords. Thesystem is completed with the applanation lens set, tonometer, corneal storage jar, optical zonemarker, spatula, stop attachment, and digital thickness gauge.

Microkeratomes Used in the Clinical Trial:

The microkeratomes used in the LADARVision®4000 System clinical trial included the BD K-40001 (manufactured by Becton-Dickinson), Hansatome 2 (manufactured by Bausch & Lomb),and the Moria3 CB and LSK (manufactured by Moria).

BD K-4000 TM of Becton, Dickinson and CompanyHansatome Reg. TM of Bausch & Lomb Incorporated3Moria Reg, TM of Moria SA

Page 6 of 52 7260-0107 Rev. A


C. CUSTOMCORNEAM SURGERY PLANNING SOFTWARE

The CustomCornea® Surgery Planning Software is a stand-alone computer application linkingthe diagnostic wavefront data from the WMD with the surgical treatment on the LADAR6000System. The planning software allows refinement of surgical parameters within the approvedwavefront-guided indication for the LADAR6000TM System, calculates ablation depth, checks fortreatment eligibility, and exports all messages and warnings to the excimer laser system.

After completing the surgery planning tasks, the planned treatment file is transferred to theLADAR6000 TM System. The LADAR6000' m System software imports the treatment file,calculates the excimer treatment pattern, and performs the surgery.

D. LADAR6000 T h EXCIMER LASER SYSTEM

The LADAR6000 TM System excimer laser beam is of Gaussian profile and small in diameter(<0.90mm). Corneal sculpting is achieved by delivering hundreds to thousands of excimer laserpulses to the eye in a complex pattern of spatially overlapping spots, and precision of thisprocess depends on accurate placement of the laser pulses. The LADAR6000 Tm Systemincorporates the LADARTracker® closed-loop eye-tracking system to track and compensate forpatient eye motion, including saccadic movements, during procedures so that each excimer laserpulse is delivered to the appropriate location on the cornea.

Excimer Laser Characteristics

The ultraviolet laser used in the LADAR6000 Th System is an argon fluoride excimer laser. Thislaser produces 12 nanosecond pulses of ultraviolet radiation at a wavelength of 193 nanometers.The laser repetition rate is approximately 92 pulses per second. Characteristics of the laser beamat the corneal treatment plane are shown below:

Treatment Plane Characteristics of the LADAR6000"' System Excimer Laser Beam

Pulse energy (mJ) 2.4 - 3.0Beam diameter (mm) a < 0.90Average fluence (mJ/cm 2) b 180-240

Note (a): The Gaussian beam diameter is defined as the mean of the semi-major and semi-minor axes of theelliptical beam cross-section and is the lI/e width in the Gaussian fluence distribution.

Note (b): This is the calculated average value per pulse of the laser fluence over the ablated area.

Additional features of the LADAR6000 TM Excimer Laser System include:

Optical Transmission S. stem

The excimer laser passes through an optical telescope, followed by reflection off a series ofmirrors which position the excimer laser pulses in the correct locations at the treatment plane.Tracking mirrors also compensate for patient eye motion, as detected by the LADARTracker®system.

7260-0107 Rev A Page 7 of 52


Energy Monitoring/Control

An energy monitor is mounted at the output of the LADAR6000 TM System. Prior to treatment,this energy monitor ensures that the laser pulse energy delivered to the eye will be between 2.4and 3.0 mJ. During treatment, the detector monitors laser operation.

Gas Handling

The excimer laser enclosure holds the laser, gas bottle, and gas-plumbing manifold. The gasbottle contains the pre-mixed excimer laser gas, which contains neon as the buffer gas, inaddition to argon and fluorine. The initial pressure in the gas bottle is 2000 PSI. The outletnozzle of the gas bottle contains a flow restrictor valve. Gas from the bottle flows to a fluorine-compatible gas regulator, which reduces the line pressure to 90 PSI. Two gas lines exit theregulator. One leads directly to the outlet line of the laser enclosure. In the event of a diaphragmfailure, excimer gas will flow from the regulator down this line and out of the enclosure. Outsidethe laser enclosure, the gas flows through a charcoal-based filter (to remove the F 2) beforeventing into the room. The second gas line exiting the regulator leads to the excimer lasercavity. At the line connection to the cavity there is a solenoid valve, which responds tocommands from the laser control electronics board. A second solenoid valve exists at the gasoutlet port of the laser cavity. The outlet gas line also leads out of the laser enclosure andthrough the charcoal filter.

Eye Tracking System

The LADAR6000 TM System utilizes the LADARTracker® active closed-loop eye tracking systemto track and compensate for eye motion during refractive laser surgery. The word "active" hereis used to denote two important characteristics of the device. First, the LADARTracker® systemactively tracks the position of the eye by irradiating it with pulses of 905 nm infrared "eye-safe"energy and analyzing characteristics of the returning laser radiation. This measurement occurs4000 times each second in order to detect even rapid eye motion before significant movement ofthe cornea has occurred.

The LADARTracker® system is also "active" in the sense that it actively compensates fot thedetected motion, rather than simply disabling the treatment laser when the eye position exceedssome tolerated error range. The LADARTracker ® system includes two mirrors that arecontinually repositioned to keep the eye centered in the field of view of the treatment laser. Anindependent set of mirrors is used to translate the treatment beam around within this field ofview, delivering the ablation pulses to the cornea in a predetermined spatial pattern. Thecombined system allows for each ablation pulse in the complex pattern to be delivered to theappropriate corneal site, even in the presence of substantial eye movement.

The LADARTracker® system is designed so that precise mirror movements during the course ofeach surgery are recorded. Because the geometry involved is known, exact eye movements canbe calculated from the compensatory movements of the mirrors. It is not possible to performsurgery using the LADAR6000T' System without the LADARTracker® system engaged, and nopatient has ever been treated without concurrent tracking.

Page 8 of 52 7260-0107 Rev. A


Operating Microscope

The stereo viewing operating microscope is located in the optics head. The dual optical paths areindependent of the excimer beam path and the LADARTracker® System mirrors. Oblique,omni-directional microscope lighting on either side of the system output window provides visibleillumination of the treatment plane. The operating microscope optical system is completelyindependent from the eye tracking optical system and does not provide "tracked" imagery of thepatient eye.

Fixation Target

A visible fixation target is mounted in the system to facilitate the patient looking in the directionof the treatment excimer beam. The fixation target consists of a light emitting diode (LED), apinhole aperture, an edge-illuminated reticule, and a lens. The lens, in combination with a300mm focal length achromat in the operating microscope optical path, places the LED atinfinity focus from the patient's perspective. The edge-illuminated reticule is a clear, flat etchedglass with two sets of horizontal lines. For proper eye alignment, the patient is instructed to shiftposition until the LED pinhole light is centered within the ring of white lights and then tomaintain that fixation during treatment.

Moveable Bed

A motorized patient bed, which moves on X, Y and Z axes, smoothly and rapidly positions thepatient and facilitates bilateral procedures. The bed controls are located on the Control Consoleand the Control Module. The longitudinal motion range is approximately 15", so that the patientcan lie on the bed and then be moved into position under the laser head. The lateral range ofmotion is 4", allowing surgery to be performed on either eye. The vertical range of motion is 3'.allowing adjustment for the proper distance from the laser aperture to the eye for varying headsizes. Each axis has a continually variable speed control for coarse and fine positioning.

Cross Beam Patient Positioning

Cross beam Class I lasers are used to place the cornea at a predetermined height for properablation. The cross beam laser sub-system consists of two laser line generators attached to theleft and right sides of the upper optical module. The laser diode sources produce 0.9 mwattseach at 633nm. The beam of each red-wavelength laser is transmitted through an absorptiveneutral density filter, which attenuates the laser by 97%, and a polarizer. The output of eachpolarizer is reflected off a stationary fold mirror. The two mirrors are aligned such that the twobeams are vertically aligned (one above the other) on the left sclera/limbus boundary when theapex of the cornea is 8 inches below the laser output window. This provides the operator/surgeonwith an easy method of setting the height of the patient's eye during centration and surgery.

7260-0107 Rev. A Page 9 of 52

CustomCornea* LASIK Physician's Booklet - Mixed Astigmatism

The maximum laser power at the eye is less than 15 gwatts for each laser. The lasers areseparated by 103mm and are 209mm from the eye. With this geometry, the laser spots areseparated on the retina by several times their diameter so the energy is not additive. Given thewavelength and power, the maximum permissible Class Iexposure duration is 4 minutes and 30seconds. When the cross beam lasers are turned on, a 2-minute automatic time out is activated toensure the safe exposure limit is not exceeded. The cross beam lasers comply with Class Iaccessible emission limits for laser radiation in 21 CFR 1040 as well as ANSI Z136.1-1993.

Plume Removal System

The plume removal system is housed within the calibration stage. During surgery, the plumeremoval system is deployed to a pre-determined height and provides a constant level of plumeremoval during ablation. The plume is evacuated to a filter cartridge that is contained within thesystem. This filter cartridge is inspected and replaced during preventative maintenanceperformed by Alcon Technical Service Personnel.

System Software

The LADAR6000 TM System software controlling the proprietar, excimer laser runs on an IntelPentium4-based personal computer under a Microsoft Windows operating system. The softwareenables the user to:

* properly center the treatment;

* make adjustments in the X and Y axes;

* adjust for cyclotorsion and correctly reference astigmatism; and

* place a hinge guard to protect the flap during surgery.

In addition, the software enables the user to properly match the alignment of the wavefront mapto the ablation.

Laser Shot Patterns

The LADAR6000 'T System software calculates the "laser shot pattern," i.e., the number ofexcimer laser pulses to deliver to the eye and the required position of each pulse on the cornea,based on the desired refractive correction and the current laser calibration. The system softwarealso calculates a sequence to fire the pulses in the shot pattern such that no corneal site isrevisited by the excimer beam for a finite interval. The laser firing sequence is designed toprovide a gradual corneal curvature from the starting surface shape to the corrected final profile.

Rather than the refractive correction being entered manually by the physician based on phoropterrefraction, the CustomCornea® treatment requires that the pre-operative aberrations in the eye bemeasured with a wavefront measurement device. The treatment is based on Zernike data derivedfrom a wavefront measurement device, including treatment of lower-order sphere andastigmatism components and higher-order components, such as coma and spherical aberration.

4Intel and Pentium Reg. TM of Intel Corporation5 microsoft and Windows Reg. TM of Microsoft Corporation

Page 10 of 52 7260-0107 Rev. A


The electronic file that the LADAR6000 TM System receives from the wavefront measurementdevice includes the following information:

• Patient information, including name, identification number, and clinical prescription.

* Eye information, including OD/OS and the geometric relationship of the wavefront data tothe limbus and to the pupil center.

* Wavefront information, including a Zemike polynomial representation of the wavefront andthe physical radius of that description.

The excimer laser beam characteristics (i.e., pulse energy, firing rate, fluence distribution at thetreatment plane) are the same for Conventional and CustomCornea®. treatment modalities. TheConventional LADAR6000 System treatment utilizes sphere, cylinder and axis componentsentered manually by the operator to generate the ablation profile. The CustomCornea® LASIKshaping algorithm utilizes aberration information unique to a given eye that is obtained from theWMD to guide the ablation of the cornea. The wavefront information is registered to theanatomical geometry of the eye using the WMD while the patient is sitting upright. Thisregistered alignment information is passed to the LADAR6000 System, which both permits forthe compensation of this alignment information due to the natural cyclotorsion incurred when thepatient assumes a prone position and uses the geometry information to accurately position thecustomized ablation profile on the eye.

CustomCorneao Ablation Zones

For CustomCornea® ablations, the standard optical zone is 6.5mm with a blend zone of 1.25mmfor a total ablation zone of 9.0mm.

Safety

The LADAR6000*T System contains a Class IV laser that conforms to the US FDA 21 CFR 1040Radiological Health requirements. The laser system was designed to meet the following safetyrequirements:

* UL60601-1 · EN60101-1-2* CSA 601.1 * EN 60601-1-4* ANSI/ESNA RP-27.1 · EN 60101-2-22* EN 60601-1 · EN 60825-1

NOTE: Additional details regarding operation of this laser can be found in the LADAR6000 TM

Excimer Laser System Operation Manual.

Comparable Devices

The LADAR6000 TM Excimer Laser System is functionally equivalent to the LADARVision'4000Exciiner Laser System. Clinical studies conducted with the LADARVision®4000 System areapplicable to the LADAR6000 TM System.

7260-0107 Rev. A Page 11 of 52


3. INDICATIONS, CONTRAINDICATIONS, WARNINGS,PRECAUTIONS, ADVERSE EVENTS AND COMPLICATIONS

A. INDICATIONS FOR USE

The LADAR6000 Tm Excimer Laser System is indicated for wavefront-guided Laser Assisted In-Situ Keratomileusis (LASIK):

* for the reduction or elimination of mixed astigmatism of 1.00D to less than 5.OODcycloplegic cylinder magnitude at the spectacle plane, which is greater than the spheremagnitude, and the cylinder and sphere have opposite signs;

* in patients who are 21 years of age or older; and* in patients with documented stability of refraction for the prior 12 months, as

demonstrated by a change in sphere and cylinder of less than or equal to 0.50D.

B. CONTRAINDICATIONS

Wavefront-guided LASIK is contraindicated in:

* pregnant or nursing women.

* patients with autoimmune, collagen vascular, or immunodeficiency diseases.* patients with signs of keratoconus.* patients who are taking one or both of the following medications: isotretinoin (Accutane6)

or amiodarone hydrochloride (Cordarone 7).

C. WARNINGS

Wavefront-guided LASIK is not recommended in patients who have:

* diabetes.

* a history of herpes simplex or herpes zoster keratitis.

* significant dry eye that is unresponsive to treatment.

* severe allergies.

A minimum pre-operative pupillary dilation of 7mm and a maximum dilation of I Imm must beachieved and maintained in all patients throughout the refractive procedure to optimize trackingperformance.

6,Accutane Reg. TM of Hoffmnann-La Roche Inc.7 Cordarone Reg. TM of Sanofi-Aventis

Page 12 of 52 7260-0107 Rev. A


D. PRECAUTIONS

The safety and effectiveness of the LADAR6000 TM System for wavefront-guided LASIKcorrection of mixed astigmatism have NOT been established in patients:

* with unstable mixed astigmatism.

* with ocular disease, corneal abnormality, previous corneal or intraocular surgery, ortrauma in the ablation zone.

* with a residual posterior stromal corneal thickness less than 250 microns at thecompletion of ablation.

* with a history of glaucoma.

* who are taking the medication sumatripin succinate (lmitrex 8).

* under 21 years of age.

* over the lohg term (more than 9 months after surgery).

* for treatments of mixed astigmatism of less than 1.00D cycloplegic cylinder magnitude orfor 5.OOD or greater cycloplegic cylinder magnitude.

• for retreatment with wavefront-guided LASIK.

The safety and effectiveness of wavefront-guided CustomCornea® LASIK have only beenestablished for an optical zone of 6.5mm and an ablation zone of 9.0mm.

Pupil size should be evaluated under mesopic illumination conditions. Patients with largemesopic pupils > 6.5mm (optical zone size) should be advised of the potential for negativeeffects on vision after surgery, such as glare, halos, and nighttime driving difficulty.

Preoperative evaluation for dry eye should be performed. Patients should be advised of thepotential for dry eyes post-LASIK surgery.

The physician's adjustment of defocus has not been studied, and its effects on the safety andeffectiveness outcomes of this procedure are unknown.

Please be advised that eyes with prior intraocular or corneal surgery of any kind were excludedfrom clinical trials with the LADARVision®4000 System. Safety and effectiveness, as well astracking performance, have not been established for such eyes. Although the tracking systemmay acquire track in surgically altered eyes prior to ablation, the optics of the eye may change inthe context of the ablation to potentially interfere with further tracking and compromise thecompletion of the ablation. Medical judgment should be exercised in the use of theLADAR6000TM System in pseudophakic patients and others who have had prior intraocular orcorneal surgery.

I mitrex Reg. TM of Glaxo Group Limited

7260-0107 Rev. A Page 13 of 52

'$1


E. ADVERSE EVENTS AND COMPLICATIONS

Cumulative adverse events and complications reported at any postoperative visit up to9 months in the clinical study for CustomCornea® LASIK correction of mixed astigmatism aresummarized in Table 1. The data meet the safety criteria established in the FDA GuidanceDocument of less than 1% occurrence of each type of adverse event and less than 5% overall.

Table 1. Summary of Adverse Events and ComplicationsAt Any Postoperative Visit

ADVERSE EVENTS n/N %

Miscreated flap (related to microkeratome) 2/i 1l t 1.8%

Comeal infiltrate (related to viral epidemic keratoconjunctivitis) 1/110 0.9%

COMPLICATIONS

Grade Ž I Superficial Punctate Keratitis (SPK) at one month or later 11/110 10.0%

Epithelium in the interface 6/111t 5.4%

Diffuse lamellar keratitis (DLK) 5/110 4.5%Pain at one month or later 2/110 1.8%

Foreign body sensation at one month or later 1/110 0.9%

t One eye did not receive laser ablation after the miscreated flap and was not included inthe analysis of eyes receiving laser treatment (N=1 11).


* corneal edema at one week or later;

• corneal epithelial defect (central or peripheral) at one month or later;

* decrease in best spectacle corrected visual acuity (BSCVA) of more than 10 letters (> 2lines) not due to irregular astigmatism, as shown by hard contact lens refraction at sixmonths or later;

* epithelium in the interface with a loss of BSCVA of 2 or more lines;* intraocular pressure increase of more than 10 mmHg above baseline;· intraocular pressure of more than 25 mmHg;

· late onset ofcorneal haze at six months or later with a loss of BSCVA of 2 or more lines:* melting of the flap;

* misaligned flap;* retinal detachment; and* retinal vascular accident.

Page 14 of 52 7260-0107 Rev. A


4. CLINICAL STUDY

A. INTRODUCTION

The study in the U.S. using the LADARVision®4000 System began as a prospective,randomized, unmasked, and multi-center trial, where one eye of the patient receivedCustomCornea ® LASIK correction using data from a wavefront system and the fellow eyereceived a Conventional treatment based on phoropter cycloplegic refraction. For this initialsubgroup of patients, the fellow eye served as a contralateral control.

Upon providing data to support expansion of the number of patients for enrollment, the U.S.study design was changed to a prospective, non-randomized, unmasked, and multi-center trialwhere one or both eyes of a patient received wavefront-guided CustomCornea® treatment. Theprimary control was the preoperative state of the treated eye for comparison to postoperativeoutcomes. An equivalent study design was also in progress under a Canadian protocol. Datafrom the U.S. and Canadian studies were pooled since both protocols were equivalent in terms ofthe inclusion and exclusion criteria, study procedures, patient measurements, and the treatmentapplied to the eye.

The objective of the multi-center clinical investigation was to establish safety and effectivenessof wavefront-guided CustomCornea® LASIK correction of mixed astigmatism. Patients werefollowed at I day, I week, and 1, 3, 6, and 9 months postoperatively. All eyes were required tobe treated for a target of emmetropia. All surgeries performed in the study were subject toapproval by the Sponsor.

Recruited patients had the study details and follow-up requirements explained to them and wereasked to sign an Informed Consent Document preoperatively. To be eligible for the study, mixedastigmatic patients must have had a preoperative cycloplegic refraction at the spectacle plane of> O.OOD to +6.OOD sphere with < O.OOD to -6.OOD astigmatism (minus cylinder convention) withan absolute cylinder magnitude greater than the sphere magnitude. Enrollment of mixedastigmatic eyes in the study occurred over the preoperative cycloplegic refractive range of+0.25D to +4.25D sphere with -1.00D to -6.OOD astigmatism and -1.38D to +1.63D sphericalequivalent (SE).

Stability of refraction must have been established and documented using previous clinicalrecords or measurement of spectacles. Stability was demonstrated by a change in the manifestsphere and cylinder over the prior 12 months of less than or equal to 0.50D. If a year-oldrefraction was not available, the change in refraction must have been 0.50D or less per year sincethe last documented refraction in both the manifest sphere and cylinder to a 1.00D maximum SEchange.

The manifest and cycloplegic refraction measured at the preoperative examination must havebeen within 1.00D of each other in the sphere and cylinder components. In addition, thecycloplegic refraction could not differ by more than 1.00D in sphere or cylinder from theattempted correction determined by the wavefront system.

For the contralateral treatment group, the cycloplegic refraction between the patient's two eyescould not differ by more than 1.00D in sphere or cylinder. In addition, patients must have beenwilling to have LASIK correction in both eyes within a 2-week period. These two criteria werenot applicable to patients treated under the bilateral CustomCornea® treatment study design.

7260-0107 Rev. A Page 15 of 52


Patients must have been at least 18 years of age and had a BSCVA of 20/25 or better in theoperative eye(s). Patients must have been willing to return for scheduled follow-up examinationsfor 9 months after surgery and have their eyes pharmacologically dilated at the required visits.

Patients who were contact lens wearers were requested to discontinue contact lens wear for aminimum of 2 weeks.for soft contact lenses and 3 weeks for hard contact lenses (RGP/PMMA)prior to the preoperative examination. Patients who had previously worn hard lenses wererequired to have two examinations conducted 2 to 3 weeks apart to show stability of refractionwithout lens wear. Prior to surgery, patients were not to wear their contact lenses in theoperative eye(s) for 2 to 3 weeks for soft and hard contact lenses, respectively.

Patients who exhibited any of the following conditions were excluded from the study:

* previous corneal, intraocular, or strabismus surgery in the operative eye(s)* history of or active clinically significant or vision threatening ocular disease or pathology* clinically significant corneal scar within the ablation zone or corneal abnormality such as

recurrent erosion or severe basement membrane disease• signs of keratoconus* irregular corneal astigmatism· history of herpes keratitis* autoimmune or connective tissue disease, clinically significant atopic syndrome, or

diabetes* use of chronic systemic corticosteroids or other immunosuppressive therapy* use of systemic medication with significant ocular side effects* pregnant or nursing* use of ophthalmic medications other than artificial tears for treatment of an ocular

pathology* severe dry eye syndrome unresolved by treatment• known allergy to study medications• glaucoma or glaucoma filtering surgery• participation in another ophthalmic clinical trial* calculated residual posterior stromal thickness of less than 250 microns• inability to achieve a pupillary dilation ofŽ> 7mm* at risk of angle closure* an inability to obtain a clear and complete wavefront image

The primary effectiveness parameters for this study were: improvement of uncorrected visualacuity (UCVA); predictability and stability of manifest refraction spherical equivalent (MRSE)and manifest cylinder; reduction of wavefront error, including higher-order aberrations; andpatient satisfaction. The safety parameters for this study were: preservation of BSCVA; absenceof significant findings in slit lamp and fundus examination; absence of significant intraocularpressure (lOP) elevation; and incidence of complications and adverse events.

Page 16 of 52 7260-0107 Rev. A

CustomComea ® LASIK Physician's Booklet - Mixed Astigmatism

B. RESULTS

1. Demographics

A total of 110 eyes of 63 patients were enrolled in the Primary Cohort. The demographics of thestudy population (Table 2) were typical for a refractive surgery trial performed in the U.S. Themean + standard deviation patient age was 40.6 ± 10.7 years with a range from 20 to 60 years.The majority of patients were Caucasian (94.5%) and the remaining patients were Hispanic(3.6%) and Indian (1.8%). Slightly more females (53.6%) than males (46.4%) participated in thestudy. The distribution of right and left eyes that received treatment was approximately equal(49.1% vs. 50.9%). While most patients (64.5%) did not wear contact lenses prior to surgery,32.7% wore soft contact lenses and 2.7% wore rigid gas permeable (RGP) lenses.

Table 2. Demographics

110 Eyes of 63 Enrolled PatientsAge (In Years)

Average ± Standard Deviation 40.6 + 10.7Minimum to Maximum 20 to 60

Race N % EyesCaucasian 104 94.5%

Hispanic 4 3.6%Indian 2 1.8%

Gender Female 59 53.6%Male 51 46.4%

Eye Left 56 50.9%Right 54 49.1%

Contact Lens History None 71 64.5%Soft 36 32.7%

Rigid Gas Permeable (RGP) 3 2.7%

2. Accountability

The accountability for this study was > 98.2% at all postoperative intervals (Table 3).Postoperative data were available for 110 eyes (100%) up to 6 months and for 108 eyes (98.2%)at 9 months. One patient (2 eyes) missed the 9-month visit because the patient moved out of thecountry prior to the opening of the 9-month visit window.

Table 3. Accountability at Each Visit

1 MONTH 3 MONTHS 6 MONTHS 9 MONTHSTotal Eyes Enrolled n 110 110 110 110

n 110 110 110 108Available for Analysis ItIo1010% 100.0% 100.0% 100.0% 98.2%

Unavailable Missed Visit n 0 0 0 2% 0.0% 0.0% 0.0% 1.8%

% Accountability= 000.0 100.0% 98.2%[available/(available + unavailable)] % 1000.%0.%92

7260-0107 Rev A Page 17 of 52

f t/


3. Preoperative Cycloplegic Refraction Parameters

The study population of mixed astigmatic eyes had a preoperative cycloplegic cylindermagnitude greater than the sphere in minus cylinder convention. Preoperative cycloplegicrefractive range was +0.25D to +4.25D sphere with -1.OOD3 to -6.OOD) cylinder and -1.38D) to±1 .63D spherical equivalent. The mean ± standard deviation for the preoperative cycloplegicrefraction was +1.50D ± 0.94D sphere, -2.90D) ± 1.20D cylinder and -i-.06D + O.65D sphericalequivalent. Table 4 displays the number of eyes stratified by preoperative cycloplegic sphere andcylinder. Table 5 displays the number of eyes stratified by preoperative cycloplegic sphericalequivalent and cylinder.

Table 4. Preoperative Cycloplegic Refraction Stratified by Sphere and Cylinder


SPHERE (D) -1.00 to -2.00 to -3.00 to -4.00 to -5.00 to TOTAL______________ -1.99 -2.99 -3.99 -4.99 -6.00 _____

> 0.0 to +0.99 n/N 15/110 14/110 7/110 0/110 0/110 361110% I13 .6% 12.7% 6.4% 0.0% 0.0% 32.7%

+I.Oto+19 n/N 9/110 19/110 10/110 3/110 0/110 41/110% 8.2% 17.3% 9.1% 2.7% 0.0% 37.3%

+2.Oto+29 n/N 0/110 4/110 6/110 9/110 4/110 23 /11 I0% 0.0% 3.6% 5.5% 8.2% 3.6% 20.9%

+3.00 to +3.99 n/N 0/110 0/1 10 2/110 5/110 2/110 9/110____________ % 0.0% 0.0% 1.8% 4.5% 1.8% 8.2%

+4.O0 to +5.00 n/N 0/110 0/110 0/110 0/110 1/110 1/0____________% 0.0% 0.0% 0.0% 0.0% 0.9% 0.9%

TOTAL n/N 24/110 37/1 10 25/110 17/110 7/110 10/0%-/- 21.8% 33.6% 22.7% 115.5% 6.4% 100.0%

D= Diopter

Table 5. Preoperative Cycloplegic Refraction Stratified by Spherical Equivalentand Cylinder

CYLINDER MAGNITUDE (DI) IN MINUS CYLINDER CONVENTIONSPHERICAL -1.00 to -2.00 to -3.00 to -4.00 to -5.00 to TOTALEQUIVALENT DLJ -1.99 -2.99 -3.99 -4.99 -6.00 _____

-l.00 to -2.00 n/N 0/110 1/110 5/110 2/110 0/110 8/110____________ 0.0% 0.9% 4,5% 1.8% 0.0% 7.3%

n/N 9/110 19/110 11/110 3/110 3/110 45/1100.00 to -0.99 %~ 8.2% 17.3% 10.0% 2.7% 2.7% 40.9%

+0.01 to +0.99 n/N 15/I 10 15/I 10 4/110 9/110 2/110 4511 10% 13.6% 13.6% 3.6% 8.2% 1.8% 40.9%

+L00to +.00 n/N 0/110 2/110 5/110 31110 2/110 12/1 101.00 t +2.00 %~ 0.0% 1.8% 4.5% 2.7% 1.8% 10.9%

TOTAL n/N 2F4/11IO 37/110 25/110 17/110 7/110 I 10/1TOTAL ~ % 21.8% 33.6% 22.7% 65.4% 100.0%

I= -Diopter

Page 18 of 52 7260-01 07 Rev. A

Custom~ornea ® LASIK Physician's Booklet - Mixed Astigmatism

4. Key Effectiveness Outcomes


The key effectiveness outcomes for UCVA and accuracy of MRSE and manifest cylinder areshown by visit in Table 6. These parameters at 3 and 6 months are also shown stratified bypreoperative cycloplegic cylinder in Table 7 and by preoperative cycloplegic refraction sphericalequivalent (CRSE) in Table 8.

The effectiveness data meet the criteria established in the FDA Guidance Document for at least85% of eyes achieving a UCVA of 20/40 or better and accuracy of MRSE within 0.50D ofintended in at least 50% of eyes and within 1.00D in 75% of eyes at all postoperative intervals.

Table 6. Summary of Key Effectiveness Parameters Over Time

Effectiveness Parameters I MONTH 3 MoNTHs 6MONTHS.MT 9 MONSn/N 68/94 60/94 67/94 64/92U CVA 20/20 or better if72.3% 63.8% 71.3% 69.6%

SC (62.2, 81.1) (53.3, 73.5) (61.0, 80.1) (59.1, 78.7)n/N 70/110 62/110 70/110 66/108

UCVA 20/20 or better % 63.6% 56.4% 63.6% 61.1%C1 (53.9, 72.6) (46.6, 65.8) (53.9, 72.6) (51.3, 70.3)n/N 95/110 89/110 96/110 91/108

UCVA 20/25 or better % 86.4% 80.9% 87.3% 84.3%CI (78.5, 92.2) (72.3, 87.8) (79.6, 92.9) (76.0, 90.6)n/N 106/110 105/110 108/110 101/108

UCVA 20/40 or better % 96.4% 95.5% 98.2% 93.5%i__________________________ Cl (91.0, 99.0) (89.7, 98.5) (93.6, 99.8) (87.1, 97.4)


C1 (62.4, 80.0) (61.5, 79.2) (67.3, 83.9) (65.7, 82.8)


Ci (88.5, 98.0) (86.2, 96.8) (83.9, 95.6) (81.4, 94.1)n/N 109/110 109/110 110/110 108/108

MRSE ± 2.OOD of intended % 99.1% 99.1% 100.0% 100.0%el (95.0, 100.0) (95.0, 100.0) (96.7, 100.0) (96.6, 100.0)

n/N 71/110 73/110 71/110 66/108% 64.5% 66.4% 64.5% 61.1%

of intended Cl (54.9, 73.4) (56.7, 75.1) (54.9, 73.4) (51.3, 70.3)

n/N 96/110 100/110 98/110 95/108Cylintender mantd •I.O % 87.3% 90.9% 89.1% 88.0%of intended

CI (79.6, 92.9) (83.9, 95.6) (81.7, 94.2) (80.3, 93.4)n/N 108/110 109/110 109/110 107/108

Cylinder magnitude 2.OOD % 98.2% 99.1% 99.1% 99.1%of intendedof intended _______________ Ci (93.6, 99.8) (95.0, 100.0) (95.0, 100.0) (94.9, 100.0)

UCVA = Uncorrected Visual Acuity BSCVA = Best Spectacle Corrected Visual AcuityMRSE = Manifest Refraction Spherical Equivalent Cl = 95% Confidence Interval D = Diopter

7260-0107 Rev. A Page 19 of 52


Table 7. Summary of Key Effectiveness Parameters at 3 and 6 MonthsStratified by Diopter (D) of Preoperative Cycloplegic Cylinder

_3 MoEffectiveness Parameters -1.00 to -2.00 to -3.00 to -4.00 to -5.00 to TotatEffectiveness Parameters I-1.99 -2.99 3 4 -6.00

UCVA 20/20 or better if n/N 16/22 20/36 18/23 5/9 1/4 60/94Preop BSCVA 20/20 or better % 72.7% 55.6% 78.3% 55.6% 25.0% 63.8%

UCVA 20/20 or better n/N 16/24 21/37 18/25 6/17 1/7 62/110% 66.7% 56.8% 72.0% 35.3% 14.3% 56.4%UCVA 20/25 or better n/N 24/24 28/37 23/25 12/17 2/7 89/110

UCVA20/25 r% 100.0% 75.7% 92.0% 70.6% 28.6% 80.9%

UCVA 20/40 or better n/ 24/24 33/37 25/25 17/17 6/7 105/I10_________ 100.0% 89.2% 100.0% 100.0% 85.7% 95.5%

M Edn/N 23/24 25/37 17/25 9/17 4/7 78/110MRSE ± 0.50D of %_________ 95.8% 67.6% 68.0% 52.9% 57.1% 70.9%

n/N 24/24 35/37 23/25 14/17 6/7 102/110MRSE+± l.OODof intendedMRSE ± _____1)_ofintended % 100.0% 94.6% 92.0% 82.4% 85.7% 92.7%MRSE ± 2.00D of intended n/N 24/24 37/37 25/25 16/17 7/7 109/110

_% 100.0% 100.0% 100.0% 94.1% 100.0% 99.1%Cylinder magnitude < 0.50D n/N 20/24 25/37 14/25 13/17 1/7 73/110of intended % 83.3% 67.6% 56.0% 76.5% 14.3% 66.4%Cylinder magnitude < LOOD n/ 24/24 36/37 23/25 14/17 3/7 100/110of intended % 100.0% 97.3% 92.0% 82.4% 42.9% 90.9%Cylinder magnitude < 2.001) n/N 24/24 37/37 25/25 17/17 6/7 109/110of intended % 100.0% 100.0% 100.0% 100.0% 85.7% 99.1%

6 MONTHS-1.00 to -2.00 to -3.00 to -4.00 to -5.00 toEffectiveness Parameters I Total

-1.99 -2.99 -3.99 -4.99 -6.00UCVA 20/20 or better if n/N 21/22 19/36 20/23 7/9 0/4 67/94Preop BSCVA 20/20 or better % 95.5% 52.8% 87.0% 77.8% 0.0% 71.3%

UCVA 20/20 or better n/ 21/24 20/37 20/25 9/17 0/7 70/110% 87.5% 54.1% 80.0% 52.9% 0.0% 63.6%n/N2obt 24/24 29/37 25/25 14/17 4/7 96/110

UJCVA 20/250or betterIn/ I I% 100.0% 78.4% 100.0% 82.4% 57.1% 87.3%

UCVA 20/40 or be nN 24/24 35/37 25/25 17/17 7/7 108/110________________tter __ % 100.0% 94.6% 100.0% 100.0% 100.0% 98.2%

MRSE ± OSOD of intended r/N 24/24 28/37 18/25 10/17 4/7 84/110%__87 100.0% 75.7% 72.0% 58.8% 57.1% 76.4%MRSE ± 1.000 of intended n/N 24/24 34/37 22/25 14/17 6/7 100/110

% 100.0% 91.9% 88.0% 82.4% 85.7% 90.9%M E2dn/N 24/24 37/37 25/25 17/17 7/7 110/110

MRSE ± 2.O of intended__ % 100.0% 100.0% 100.0% 100.0% 100.0% 100.0%Cylinder magnitude <s0.500 n/N 19/24 24/37 15/25 11/17 2/7 71/110of intended % 79.2% 64.9% 60.0% 64.7% 28.6% 64.5%Cylinder magnitude < lOO0D n/N 23/24 35/3 7 2 4/21.5 14/17 2/7 98/110of intended % 95.8% 94.6% 967. 82.4% 28.6% 89.1%Cylinder magnitude < 2.001) n/N 24/24 37/37 25/25 1/1/7 109/110of intended % 100.0% 100.0% 100.0% 100.0% 85.7% 99.1%

UGVA = Uncorrected Visual Acuity BSCVA = Best Spectacle Corrected Visual AcuityMRSE = Manifest Refraction Spherical Equivalent D = Diopter

Page 20 of 52 7260-0107 Rev A


Table 8. Summary of Key Effectiveness Parameters at 3 and 6 MonthsStratified by Diopter (D) of Preoperative Cycloplegic Refraction Spherical Equivalent

: : MONTHS:

-1.00 to 0.00 to +0.01 to +1.00 to-2.00 -0.99 +0.99 +2.00 Total

UCVA 20/20 or better if n/N 5/6 24/41 24/36 7/11 60/94Preop BSCVA 20/20 or better % 83.3% 58.5% 66.7% 63.6% 63.8%

n/N 5/8 24/45 26/45 7/12 62/110% 62.5% 53.3% 57.8% 58.3% 56.4%

UCVA 20/25 or better n/N 7/8 39/45 34/45 9/12 89/110% 87.5% 86.7% 75.6% 75.0% 80.9%

UCVA 20/40 or better n/N 8/8 43/45 43/45 11/12 105/110% 100.0% 95.6% 95.6% 91.7% 95.5%

n/N 7/8 35/45 27/45 9/12 78/110% 87.5% 77.8% 60.0% 75.0% 70.9%

n/N 8/8 42/45 41/45 11/12 102/110% 100.0% 93.3% 91.1% 91.7% 92.7%

n/N 8/8 45/45 44/45 12/12 109/110MRSE ± 2.001) of intended % 100.0% 100.0% 97.8% 100.0% 99.1%Cylinder magnitude < 0.50D n/N 4/8 30/45 32/45 7/12 73/110of intended % 50.0% 66.7% 71.1% 58.3% 66.4%Cylinder magnitude < 1.00D n/N 8/8 40/45 42/45 10/12 100/110of intended % 100.0% 88.9% 93.3% 83.3% 90.9%Cylinder magnitude < 2.00D n/N 8/8 44/45 45/45 12/12 109/110of intended % 100.0% 97.8% 100.0% 100.0% 99.1%

6 MONTHS

-1.00 to 0.00 to +0.01 to +1.00 to-2.00 -0.99 +0.99 +2.00 Total

UCVA 20/20 or better if n/N 5/6 29/41 27/36 6/11 67/94Preop BSCVA 20/20 or better % 83.3% 70.7% 75.0% 54.5% 71.3%

UCVA 20/20 or better n/N 6/8 29/45 29/45 6/12 70/110% 75.0% 64.4% 64.4% 50.0% 63.6%

UCVA 20/25 or better n/N 8/8 41/45 36/45 11/12 96/110% 100.0% 91.1% 80.0% 91.7% 87.3%

UCVA 20/40 or better n/N 8/8 44/45 45/45 11/12 108/110% 100.0% 97.8% 100.0% 91.7% 98.2%

MRSE ± OSO0D of intended / N 7/8 34/45 34/45 9/12 84/110% 87.5% 75.6% 75.6% 75.0% 76.4%

MRSE ± LOOD of intended n/N 8/8 42/45 39/45 11/12 100/110% 100.0% 93.3% 86.7% 91.7% 90.9%

MRSE ± 2.OOD) of intended n/N 8/8 45/45 45/45 12/12 110/110% 100.0% 100.0% 100.0% 100.0% 100.0%

Cylinder magnitude < 0.50D n/N 4/8 27/45 33/45 7/12 71/110of intended % 50.0% 60.0% 73.3% 58.3% 64.5%Cylinder magnitude < [O0D n/N 8/8 39/45 42/45 9/12 98/110of intended % 100.0% 86.7% 93.3% 75.0% 89.1%Cylinder magnitude < 2.00D n/N 8/8 44/45 45/45 12/12 109/110of intended % 100.0% 97.8% 100.0% 100.0% 99.1%

UCVA = Uncorrected Visual Acuity BSCVA = Best Spectacle Corrected Visual AcuityMRSE = Manifest Refraction Spherical Equivalent D = Diopter

7260-0107 Rev. A Page 21 of 52


b) Uncorrected Visual Acuity

Uncorrected visual acuity is displayed in Table 9. Preoperatively, 35.5% of eyes had a UCVA of20/40 or better. At 3 months, the UCVA was 20/20 or better in 56.4% of eyes, 20/25 or better in80.9% and 20/40 or better in 95.5%. At 6 months, the UCVA was 20/20 or better in 63.6% ofeyes, 20/25 or better in 87.3% and 20/40 or better in 98.2%. For those eyes with a preoperativeBSCVA of 20/20 or better, a UCVA of 20/20 or better was achieved in 63.8% and 71.3% of eyesat 3 and 6 months, respectively.

Table 9. Cumulative Uncorrected Visual Acuity a~t Distance

PREOP 1 MONTH 3 oI rs 6MNH MyONT.4

n/N 0/110 1/110 2/110 3/110 3/108% 0.0% 0.9% 1.8% 2.7% 2.8%n/N 0/110 8/110 11/110 11/110 9/108% 0.0% 7.3% 10.0% 10.0% 8.3%n/N 0/110 33/110 33/110 39/110 40/108% 0.0% 30.0% 30.0% 35.5% 37.0%n/N 1/110 70/110 62/110 70/110 66/108% 0.9% 63.6% 56.4% 63.6% 61.1%

20/25 or better n/N 4/110 95/110 89/110 96/110 91/108% 3.6% 86.4% 80.9% 87.3% 84.3%n/N 17/110 104/110 98/110 104/110 99/108% 15.5% 94.5% 89.1% 94.5% 91.7%n/N 39/110 106/110 105/110 108/110 101/108% 35.5% 96.4% 95.5% 98.2% 93.5%n/N 53/I 10 109/110 110/110 109/110 107/108% 48.2% 99.1% 100.0% 99.1% 99.1%n/N 68/110 110/110 110/110 110/110 107/108% 61.8% 100.0% 100.0% 100.0% 99.1%

20/80 or better n/N 84/110 110 I10 110/110 110/110 108/108% 76.4% 100.0% 100.0% 100.0% 100.0%n/N 98/I110 110/110 110/I110 110/110 108/10820/100 or better nN- /i-o-iom im/ i 0/0

2%rb 89.1% 100.0% 100.0% 100.0% 100.0%n/N 12/I 10 0/l110 0/110 0/110 0/108Worsethan 20/100 ~ 10.9% 0.0% 0.0% 0.0% 0.0%

Page 22 of 52 7260-0107 Rev. A


c) Comparison of Postoperative Uncorrected Visual Acuity and Preoperative BestSpectacle Corrected Visual Acuity

A comparison of postoperative UCVA to preoperative BSCVA after CustomCornea® LASIKsurgery is presented in Table 10 with differences based on lines of visual acuity. A postoperativeUCVA equal to or better than the preoperative BSCVA was achieved in 56.4% and 60.0% ofeyes at 3 and 6 months, respectively.

Table 10. Postoperative Uncorrected Visual Acuity Compared toPreoperative Best Spectacle Corrected Visual. Acuity

I MONTH 3iMoNTiS 6MONTHS 9 MONTHSUCVA 2 Lines Better n/N 0/110 0/110 2/110 2/108Than Preop BSCVA % 0.0% 0.0% 1.8% 1.9%UCVA I Line Better n/N 13/110 18/110 19/110 20/108Than Preop BSCVA % 11.8% 16.4% 17.3% 18.5%UCVA Equal* to n/N 53/110 44/110 45/110 43/108Preop BSCVA % 48.2% 40.0% 40.9% 39.8%UCVA I Line Worse n/N 26/110 21/110 29/110 21/108Than Preop BSCVA % 23.6% 19.1% 26.4% 19.4%UCVA 2 Lines Worse n/N 9/110 13/110 7/110 11/108Than Preop BSCVA % 8.2% 11.8% 6.4% 10.2%UCVA >2 Lines Worse n/N 9/110 14/110 8/110 11/108Than Preop BSCVA % 8.2% 12.7% 7.3% 10.2%

UCVA = Uncorrected Visual Acuity BSCVA = Best Spectacle Corrected Visual AcuityEqual visual acuity is within 2 or 3 letters on the same line of a visual acuity chart

7260-0107 Rev. A Page 23 of 52


d) Accuracy of Manifest Refraction Spherical Equivalent

As shown in Table I1, accuracy of MRSE was within 0.50D of emmetropia in 70.9% of eyes,within 1.00D in 92.7% and within 2.00D in 99.1% at 3 months. At 6 months, the MRSE waswithin 0.50D of emmetropia in 76.4% of eyes, within 1.00D in 90.9% and within 2.00D in100%. Of the eyes that did not achieve an MRSE within 1.00D of emmetropia, 5.5% at3 months and 7.3% at 6 months had more than +1.00D of hyperopia, whereas 1.8% at 3 and6 months had more than -1.00D of myopia. One eye (0.9%) had more than +2.OOD of hyperopiaby MRSE at 3 months.

Table 11. Accuracy of Manifest Refraction Spherical Equivalent

I MoNTH 3 MONTHS 6 HS 9.MONTHs* 0.50D n/N 79/110 78/110 84/110 81/108

% 71.8% 70.9% 76.4% 75.0%n/N 104/110 102/110 100/110 96/108% 94.5% 92.7% 90.9% 88.9%

* 2.OOD n/N 109/110 109/110 110/110 108/108% 99.1% 99.1% 100.0% 100.0%

> ± 2.OOD n/N 1/110 1/110 0/110 0/108% 0.9% 0.9% 0.0% 0.0%

n/N 5/110 6/11I0 8/110 9/108Postop Hyperopic MRSE > +I.00D 73% 8.30% 4.5% 5.5% 7.3% 8.3%

n/N 1/110 1/110 0/110 0/108Postop Hyperopic MRSE > +2.OOD 0.9% 0.9% 0.0 0.0%% 0.9% 0.9% 0.0% 0.0%

n/N 1/110 2/110 2/110 3/108% 0.9% 1.8% 1.8% 2.8%

n/N 0/110 0/110 0/110 0/108Postop Myopic MRSE < -2.OOD % 0.0% 0.0% 0.0% 0.0%

MRSE = Manifest Refraction Spherical Equivalent D = Diopter

Page 24 of 52 7260-0107 Rev. A


e) Accuracy of Manifest Refraction by Meridian

Accuracy of manifest refraction is displayed for the preoperative hyperopic meridian in Table 12and for the preoperative myopic meridian in Table 13. Slight undercorrection along thepreoperative hyperopic meridian was observed based on a mean correction error of +0.15D+ 0.69D at 3 months and +0.20D ± 0.63D at 6 months. Along the preoperative myopic meridian,slight undercorrection was observed based on a mean correction error of -0.09D ± 0.67D at3 months and -0.07D ± 0.61D at 6 months.

Table 12. Accuracy of Manifest Refraction in Preoperative Hyperopic Meridian

Correction Error I MONTH 3 MONTHS 6 MONTHS I 9 MONTHS

Mean ± SD (D) +0.07 ± 0.68 +0.15 ± 0.69 +0.20 ± 0.63 +0.17 ± 0.63

0.0± Dn/N 79/110 74/110 77/110 73/1080 .% 71.8% 67.3% 70.0% 67.6%

Undercorrected (Postoperative Hiyperopia)n/N 10/110 18/110 16/110 15/108> 0.50 to 1.OOD% 9.1% 16.4% 14.5% 13.9%

n/N 4/110 7/110 8/110 7/108% 3.6% 6.4% 7.3% 6.5%

n/N 2/110 2/110 2/110 2/108% 1.8% 1.8% 1.8% 1.9%

Overcorrected (Postoperative Myopia)n/N 10/110 5/110 5/110 10/108

> 0.50 to hOOD % 9.1% 4.5% 4.5% 9.3%n/N 5/110 4/110 2/110 1/108% 4.5% 3.6% 1.8% 0.9%

n/N 0/110 0/110 0/110 0/108% 0.0% 0.0% 0.0% 0.0%

Table 13. Accuracy of Manifest Refraction in Preoperative Myopic Meridian

Correction Error I MONTH 3 MONTHS 6 MONTHS 9 MONTHS

Mean ± SD (D) -0.12 ± 0.64 -0.09 ± 0.67 -0.07 ± 0.61 -0.13 ± 0.66

0.0 Dn/N 73/1 10 67/110 71/110 66/1080D% 66.4% 60.9% 64.5% 61.1%

Undercorrected (Postoperative Myopia)n/N 17/110 20/110 17/110 19/108% 15.5% 18.2% 15.5% 17.6%

n/N 6/110 5/110 5/110 6/108> 1.00 to 2.OOD% 5.5% 4.5% 4.5% 5.6%

*>2.OOD n/N 1/110 0/110 0/110 0/108_________________ 0.9% 0.0% 0.0% 0.0%

Overcorrected (Postoperative Hyperopia)n/N 9/110 I /I 10 8/110 10/108% 8.2% 10.0% 7.3% 9.3%

n/N 4/110 7/110 9/110 7/108% 3.6% 6.4% 8.2% 6.5%

> 2.OOD n/N 0/110 0/110 0/110 0/108% 0.0% 0.0% 0.0% 0.0%

SD = Standard Deviation = Diopter

7260-0107 Rev. A Page 25 of 52

'Iv'


f) Accuracy of Manifest Refraction Sphere and Cylinder Magnitude

Table 14 displays the accuracy of manifest sphere and cylinder magnitude. Postoperativemanifest sphere was within 0.50D of emmetropia in 71.3% of eyes, within 1.OOD in 87.0% andwithin 2.OOD in 98. 1% at 3 months. Manifest sphere was within 0.50D of emmetropia in 70.4%of eyes, within 1.OOD in 88.0% and within 2.OOD in 98. 1% at 6 months.

Postoperative manifest cylinder magnitude was C 0.50D of emmetropia in 66.4% of eyes,:S 1.OOD in 90.9% and < 2.OOD in 99.1% at 3 months. Cylinder magnitude was C 0.50D in64.5% of eyes, < 1.OOD in 89.1% and •- 2.OOD3 in 99.1% at 6 months.

Table 14. Accuracy of Manifest Sphere and Cylinder Magnitude

I MONTH 3 MONTHs 6 MONTHS 91MOTHSSphere" ~~~(N=108) (N=108) (N=108) __________

Postop Mean ± SD (D) +0.27 ± 0.65 +0.31 ± 0.68 +0.35 ± 0.62 +0.33 ± 0.64

Attempted Mean ± SD (D) +1.20+±0.88 +1.20 ±0.88 +1.20 ±0.88 +1.19+±0.89

Achieved Mean ± SD (D) +0.92 ± 0.98 +0.89 ± 1.03 ±0.85 + 1.00 +0.87 ± 1.04

% Achieved 69+±85 64+±79 61±+85 60 ±91± 0.50D n/N 81/108 77/lo8 76/108 77/106

% 75.0% 71.3% 70.4% 72.6%± LOOD n/N 99/108 94/108 95/108 94/106

% 91.7% 87.0% 88.0% 88.7%± 2.OOD n/N 106/10-8 10F6-/108 106/108 104/106

% 98.1-% 98.1% 98.1% 98.1%Cylinder 1 MONTH 3 MONTHS 6 MONTHS 9 MONTHSCylinder ~~(N=l11) (N= 1O) (N=11O) (N18

Postop Mean ± SD (D) -0.58 +0.55 -0.53 ± 0.53 -0.55 ±E 0.47 -0.59 ± 0.46

Attempted Mean ± SD (D) -2.89± 1,21 -2.89+± 1.21 -2.89 ± 1.21 -2.90 ± 1.21

Achieved Mean ± SD (D) -2.30± 1.12 -2.36+± 1.12 -2.34 ± 1.1$ -2.31 + 1.17

% Achieved 78+20 81 ±18 79+±18 77+±20

• OSO0D n/N 71/110 73/110 71/110 66/108% 64.5% 66.4% 64.5% 61.1%• LOOD n/N 96/1 10 100/I 10 98/1 10 95/108

% 87.3% 90.9% 89.1% 88.0%S 2OOD n/N 10---F8/1 10 -- 09/I 1-0 109/110 107/108• 2.OO982%991%991%991

*Excludes two eyes with a preoperative manifest sphere of 00.

Page 26 of 52 7260-01 07 Rev. A


g) Effectiveness of Astigmatism Correction

Effectiveness of astigmatism correction at 3 and 6 months was evaluated based on the percentagereduction in cylinder magnitude and by vector analysis (Table 15). The mean percentagereduction in absolute manifest cylinder was 80.6% at 3 months and 79.1% at 6 months with anoverall trend for a greater percentage reduction in eyes with higher preoperative cylinder. Themean correction ratio based on vector analysis of manifest cylinder was 0.92 at 3 months and0.91 at 6 months.

Table 15. Effectiveness of Astigmatic Correction By Manifest Cylinder

3 MONTHS

Preoperative Mean Percentage Reduction Vector AnalysisCylinder IN in Cylinder Magnitude Mean ± SD Correction Ratio

All 110 80.6% 0.92 ± 0.18

1.00 to < 2.00D 26 75.9% 0.86 ± 0.21

2.00 to <3.00D 34 79.9% 0.94 ± 0.17

3.00 to < 4.00D 26 84.1% 0.93 ± 0.14

4.00 to < 5.00D 16 87.1% 1.01 ± 0.12

5.00 to 6.00D 8 74.4% 0.83 ± 0.24

6 MONTHS

Preoperative N Mean Percentage Reduction Vector AnalysisCylinder in Cylinder Magnitude Mean + SD Correction Ratio

All 110 79.1% 0.91 ±0.17

1.00 to < 2.OOD 26 72.3% 0.84 ± 0.20

2.00 to <3.OOD 34 77.3% 0.92 0.17

3OO to < 4.00D 26 83.9% 0.93 + 0.16

4.00 to < 5.001D 16 87.0% 0.98 ±0.12

5.00 to 6.00D 8 78.0% 0.86 + 0.20

SD = Standard Deviation D = Diopter

Correction Ratio is the ratio of achieved vs. intended vector magnitude

7260-0107 Rev. A Page 27 of 52

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h) Refraction Over Time

Table 16 presents the manifest and cycloplegic phoropter refraction over time and the wavefrontrefraction from the wavefront measurement under cycloplegic conditions.

The mean manifest spherical equivalent was +0.03D + 0.62D at 3 months and +0.06D ± 0.57D at6 months. The mean cycloplegic and wavefront spherical equivalents were similar over time. Asexpected under cycloplegic conditions, the cycloplegic and wavefront spherical equivalentsreflected more hyperopia that was within 0.50D of the manifest spherical equivalentpreoperatively and postoperatively.

The mean manifest cylinder was -0.53D ± 0.53D at 3 months and -O.55D ± 0.47D at 6 months.The mean cycloplegic cylinder was similar to the manifest cylinder over time. The meanwavefront cylinder was within 0.25D of the manifest and cycloplegic refractions postoperatively.

Table 16. Mean Refraction Over Time

Mean ± Standard Deviation PREOP 1 MONTH 3 MONTHS 6 MONTHS 9 MONTHSManifest Refraction (D) N=1 10 N=110 N=I 10 N=1 10 N=108Spherical Equivalent -0.27 ± 0.67 -0.03 4. 0.59 0.03 ± 0.62 0.06 ± 0.57 0.02 + 0.59Cylinder -2.89 + 1.21 -0.58 + 0.55 -0.53 ± 0.53 -0.55 0.47 -0.59 + 0.46Cycloplegic Refraction (D)* N=l 10 -- N=l 10 N=108 --

Spherical Equivalent 0.06 ± 0.65 -- 0.49 ± 0.56 0.4 4 0.56 --

Cylinder -2.90 + 1.20 -- -0.49 ± 0.51 -0.52 + 0.49 --

Wavefront Refraction (D)** N-110 N=103 N=100 N=103 N=100Spherical Equivalent 0.04 ± 0.71 0.35 + 0.45 0.44 + 0.46 0.31 ± 0.46 0.39 + 0.52Cylinder -2.91 + 1.25 -0.71 ± 0.49 -0.69 ± 0.47 -0.65 + 0.35 -0.74 ± 0.52

Refractions at the spectacle plane D = Diopter* Cycloplegic refraction not required at I month and 9 months

Wavefront measurement under cycloplegic conditions with refraction analyzed over 3.5mm diameter

Page 28 of 52 7260-0107 Rev. A

52-


5. Stability of Manifest Refraction

Refractive stability was analyzed as paired differences in the non-vector manifest cylindermagnitude between consecutive visits (Table 17). Eyes with data available at each postoperativeinterval were evaluated in a 6-month consistent cohort of 110 eyes and a 9-month cohort of108 eyes.

Cylinder stability was achieved between I and 3 months with 100% of eyes demonstrating< 1.00D magnitude change and a mean change of -0.05D ± 0.29D at a rate of -0.03D change permonth for the 6-month consistent cohort. Cylinder stability was confirmed between 3 and6 months with 100% of eyes demonstrating < 1.00D magnitude change and a decrease in themean change over time to 0.02D ± 0.24D at a rate of 0.01D chahge per month. The 95%confidence interval of the mean change in cylinder magnitude overlapped between postoperativeintervals with a narrow range (<0.1 ID) between the upper and lower limits.

The 9-month consistent cohort supported the overall trends in cylinder stability observed amongthe 6-month cohort. Between all consecutive postoperative intervals, at least 99.1% of eyesshowed •< 1.00D of cylinder magnitude change. The mean change in cylinder magnitude was0.05D ± 0.25D between 6 and 9 months at a rate of 0.02D change per month.

Table 17. Stability of Manifest Cylinder Magnitude

Change in Cylinder Magnitude Between 1 and 3 Months 3 and 6 Monthsn/N 110/110 110/1106-Month < 1.00D % 100.0% 100.0%

Cohort(N=l 10) Mean Change* ± Standard Deviation -0.05 ± 0.29 0.02 ± 0.24

95% Confidence Interval of Mean Change (-0.11, 0.00) (-0.03, 0.06)Mean Change* per Month -0.03 0.01Change in Cylinder Magnitude Between 1 and 3 Months 3 and 6 Months 6 and 9 Months

n/N 108/108 108/108 107/1089-Month < LOOD % 100.0% 100.0% 99.1%Cohort(N=I08) Mean Change* ± Standard Deviation -0.05 ± 0.29 0.01 ± 0.23 0.05 ± 0.25

95% Confidence Interval of Mean Change (-0. 1, 0.00) (-0.03, 0.05) (0.00, 0.10)I Mean Change* per Month -0.03 0.003 0.02

D = Diopter* Positive value reflects an increase in magnitude and a negative value reflects a decrease in magnitude

between visits.

7260-0107 Rev A Page 29 of 52

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Similarly, refractive stability was analyzed as paired differences in MRSE between consecutivevisits for the 6-month and 9-month consistent cohorts of eyes with data available at eachpostoperative interval (Table 18).

Stability of MRSE was achieved between I and 3 months with 100% of eyes demonstrating achange in MRSE • 1.OOD and a mean change of 0.06D ± 0.29D at a rate of 0.03D change permonth for the 6-month consistent cohort. Stability was confirmed between 3 and 6 months with100% of eyes demonstrating a change in MRSE • 1.OOD) and a decrease in the mean change overtime to 0.03D + 0.25D at a rate of0O.01D change per month. The 95% confidence interval of themean change in MRSE overlapped between postoperative intervals with a narrow range(S 0.1 I D) between the upper and lower limits.

The 9-month consistent cohort showed similar MRSE stability trends to the 6-month cohort. Alleyes demonstrated a change in MRSE • L OOD between postoperative visits. Between 6 and9 months, the mean MRSE change was -0.04D ± O.26D at a rate of-40.1D change per month.

Table 18. Stability of Manifest Refraction Spherical Equivalent

Change in MRSE Between 1 and 3 Months 3 and 6 Monthsn/N 110/110 110/110

6-Month < jLOjD % 100.0% 100.0%Cohort(N=1 10) Mean Change ± Standard Deviation 0.06 + 0.29 0.03 + 0.25

95% Confidence Interval of Mean Change (0.00, 0.11) (-0.01, 0.08)________Mean Change per Month 0.03 0.01

Change in MRSE Between I and 3 Months 3 and 6 Months 6 and 9 Monthsn/N 108/108 108/lOS 108/1089-Month < iLOOD % 100.0% 100.0% 100.0%

Cohort(N=108) Mean Change±+Standard Deviation 0.06 ± 0.29 0.03 + 0.25 -0.04 + 0.26

95% Confidence Interval of Mean Change (0.00, 0.11) (-002, 0.07) (-009, 0.01)________Mean Change per Month 0.03 0.01 -0.01

D = Diopter

Page 30 of 52 7260-0107 Rev. A

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6. Wavefront Outcomes

Table 19 displays the mean change from preoperative in total root mean square (RMS) wavefronterror and in higher-order aberrations through 6th-order. The mean change in total RMSwavefiront error decreased by 64.1% at 3 months and 67.2% at 6 months from preoperative.Higher-order aberrations were not significantly changed from preoperative on average with anincrease of 2.3% at 3 months and 2.2% at 6 months. Spherical aberration decreased in magnitudeat 3 and 6 months from preoperative with a mean directional shift from positive sphericalaberration preoperatively (0.233pm) towards slightly negative spherical aberration at 3 months

(-0.OO3pm) and 6 months (-0.007pm).

Table 19. Mean Change in Aberrations Up to 6Th-Order From Preoperative*___________________ ~~~~ 3MOTS =00) ... I.1 ~ 6Mo4NTHS (N=103)~~

Aberration Mean Change Mean Change Mean Change Mean Change________________________ ~(gmn) (% ) (gtin) (% )

Total RMS Error -1.905 -64.1 -1.998 -67.2Higher-Order 0.010 2.3 0.010 2.2

Coma 0.030 12.5 0.034 1 3.9Trefoil 0.008 4.0 0.005 2.7

Spherical Aberration Magnitude f -0.1 14 -48.4 -0.101 -42.8Spherical Aberration Value t-0.236 -101.2 -0.240 -102.9

Secondary Astigmatism 0. 073 92.8 - 0.066 84.3Tetrafonil 0.023 30.4 0.027 35.3

Combined 5"' and 6"' Order 0-.037 49.5 0.035 46.6RMS = Root Mean Square Wavefront Analysis Diameter =60Omm

* Positive change represents increase from preop; Negative change represents decrease from preopt- Based on absolute spherical aberration magnitude t Based on signed spherical aberration value

At 3 and 6 months, 100% of eyes had a reduction in total RMS error from preoperative: Areduction in higher-order aberrations from preoperative was observed in 55.0% of eyes at3 months and 54.4% at 6 months (Table 20).

Table 20. Percentage of Eyes with Reduced Aberrations Up to 6 Ih-Order FromPreoperative

____________________________ 3 MONTHS (N=100) 6 MONTHS (N= 103)

Aberration % Eyes with Reduction in AberrationsTotal RMS Error 100.0% 100.0%

Higher-Order 55.0% 54.4%_________

Coma 48.0% 49.5%_________

Trefoil 49.0%456Spherical Aberration Magnitude t 80.0% 78.6%__________

Secondary! Astigmatism 18.0% ___ 17_____5 ___

Tetratoil 32.0%320Combined 5m and 6b' Order 18.0% 17.5%

RMS =Root Mean Square Wavefront Analysis Diameter =6.0mm

t Reduction in absolute spherical aberration magnitude

7260-0107 Rev A Page 31 of 52


Wavefront-guided CustomCornea® LASIK was compared to the baseline established forConventional LASIK correction of mixed astigmatism using phoropter refraction for eyes treatedunder the same study protocol over the same preoperative cycloplegic refractive range of-1.00Dto -3.50D cylinder. Wavefront aberrations at 3 and 6 months were analyzed up to 4th-order forthe Comparison Cohort (Table 21).

Compared to Conventional eyes, CustomCornea® eyes showed:

* statistically significantly lower mean amplitudes of total RMS error, higher-orderaberrations, trefoil, spherical aberration magnitude, secondary astigmatism and tetrafoil at3 and 6 months postoperatively (t-test with unequal variance; p<0.05).

• greater mean decrease in total RMS error from preoperative at.3 and 6 months.

* a mean decrease in higher-order aberrations from preoperative compared to a meanincrease for Conventional eyes at 3 and 6 months.

Spherical aberration value for the CustomComea® eyes was positive preoperatively (0.235ffm)and at 3 months (0.041[pm) and 6 months (0.029pm). Similarly for the Conventional eyes,spherical aberration value was positive preoperatively (0.176ffm) and at 3 months (0.099gm) and6 months (0.11 2pm).

Table 21. Mean Change in Aberrations Up to 4th-Order from Preoperative*:CustomCornea® vs. Conventional Comparison Cohort

3 MONTHSAberration CustomCornea®(N74) Conventional(N=26) p-

gm % Am % Value §Total RMS Error -1.509 -62.2 -0.990 -39.8 <0.0001

Higher-Order -0.060 -13.7 0.199 51.3 <0.0001Coma -0.008 -3.3 0.108 55.7 0.1542Trefoil -0.021 -11.1 0.167 91.6 <0.0001

Spherical Aberration Magnitude t -0.132 -56.0 -0.016 -8.9 0.0167Spherical Aberration Value -0.195 -82.8 -0.076 -43.4 0.1332


]__ __ 6 MONTHSAberration CustomCornea®(N=81) Conventional (N=25) p-

gm _____% gfm % Value §Total RMS Error -1.534 -63.2 -0.985 -39.6 <0.0001

Higher-Order -0.053 -12.0 0.232 59.8 <0.0001Coma -0.010 -3.9 0.135 69.5 0.0905Trefoil -0.014 -7.7 0.160 88.1 0.0001

Spherical Aberration Magnitude t -0.120 -51.1 -0.008 -4.6 0.0224Spherical Aberration Value $ -0.206 -87.5 -0.064 -36.4 0.0421


RMS = Root Mean Square Wavefront Analysis Diameter = 6.0mm* Positive change represents increase from preop; Negative change represents decrease from preopt Based on absolute spherical aberration magnitude t Based on signed spherical aberration value§ t-test with unequal variance for postoperative comparison between treatment types;

p<0.05 statistically significant, shown in boldPage 32 of 52 7260-0107 Rev. A


A vision simulation program was used to model the effect of mean higher-order aberrationmagnitudes at 3 months after wavefront-guided CustomCornea® LASIK versus ConventionalLASIK. The CustomCornea® cohort is restricted to those eyes over a comparable preoperativecylinder range to all Conventional mixed astigmatic eyes treated in the study (-1.00D to -3.50D).The difference in image blurring is comparable to a defocus error difference of approximately0.11D (i.e., 0.10D for the CustomCornea® simulation and 0.21D for the Conventionalsimulation).

The following charts (Figure 1) provide an illustration of the appearance of the visual acuitychart with glasses or contact lenses after surgery. The charts show the difference in higher-orderaberrations present in the eye after CustomCornea® LASIK (left chart) and after ConventionalLASIK (right chart).

DO NOT REPRODUCE THE CHARTS BELOW

Figure 1. Simulated chart images for the average higher-order aberrations at 3 monthsafter wavefront-guided surgery compared to after conventional surgery, based on

wavefront over a 6 mm diameter pupil.

After CustomCornea®LASIK After Conventional LASIK

P V E H R PY E H RE H V D F EH V D F

N U Z F E N U a IU H N Z R U H H R

D " E F P a OFEr U E P I P ,a fi..,t a

As shown in Table 22, more eyes had a reduction in higher-order aberrations afterCustomCornea® LASIK compared to after Conventional LASIK at 3 months (66.2% vs. 7.7%)and 6 months (61.7% vs. 8.0%).

Table 22. Percentage of Eyes with Reduced Aberrations Up to 4th Order from Preoperative:

CustomCornea® vs. Conventional Comparison Cohort

3 MoNTHS 6 MONTHs

Aberration CustomCornea® Conventional CustomCornea® Conventional(N - 74) (N = 26) (N: 81) (N = 25)

Total RMS Error 100.0% 92.3% 100.0% 96.0%Higher-Order 66.2% 7.7% 61.7% 8.0%

Coma 55.4% 19.2% 55.6% 28.0%

Trefoil 55.4% 7.7% 51.9% 20.0%Spherical Aberration Magnitude t 86.5% 57.7% 85.2% 52.0%

Secondary Astigmatism 21.6% 19.2% 19.8% 16.0%Tetrafoil 32.4% 23.1% 30.9% 20.0%

RMS = Root Mean Square Wavefront Analysis Diameter = 6.0mmt Reduction in absolute spherical aberration magnitude

7260-0107 Rev. A Page 33 of 52

[t$7

Customn~omea~ LASIK Physician's Booklet - Mixed Astigmatism

7. Key Safety Outcomes


The key safety outcomes are presented by visit in Table 23. These parameters at 3 and 6 monthsare also shown stratified by preoperative cycloplegic cylinder in Table 24 and by preoperativeCRSE in Table 25.

No eyes had a loss of more than 2 lines of BSCVA and one eye (0.9%) had a loss of 2 lines atI month. All eyes had a BSCVA within I line of preoperative BSCVA at 3 months or later.Preoperative BSCVA was 20/25 or better for all eyes. Postoperative BSCVA was 20/32 or betterat all postoperative intervals and 20/25 or better at 3 months or later.

The safety data meet the criteria established in the FDA Guidance Document of less than 5% ofeyes with a loss of more than 2 lines of BSCVA, less than 1% having a BSCVA of worse than20/40, and less than 5% having an increase in cylinder magnitude of more than 2D at allpostoperative intervals.

Table 23. Summary of Key Safety Parameters Over TimeSafety Paramete rs 1 MONTH 3 MONTHS 6 MONTHS 9 MONTHS

n/N 0/110 0/110 0/11To 0/108Loss of > 2 Lines BSCVA % 0.0% 0.0% 0.0% 0.0%

Cr (0.0,3) (0.0, 3.3) (0.0, 3.3) (0.0, 3.4)n/N 1/110 0/110 0/110 0/108

Loss of 2 Lines BSCVA % 0.9% 0.0% 0.0% 0.0%______________________________ CI (0.0, 5.0) (0.0, 3.3) (0.0, 3.3) (0.0, 3.4)

n/N 0/110 0/110 0/110 0/108BSCVA worse than 20/40 % 0.0% 0.0% 0.0% 0.0%

ci (0.0, 3.3) (0.0, 3.3) (0.0, 3.3) (0.0, 3.4)n/N 0/110 0/110 0/110 0/lOS

Increase > 2D) cylinder magnitude % 0.0% 0.0% 0.0% 0.0%Cl (0.0, 3.3) (0.0, 3.3) (0.0, 3.3) (0.0, 34

BSCVA worse than 20/25 nN 1/94 0/94 0/94 0/92if 20/0 or btter peoperaively% 1.1% 0.0% 0.0% 0.0%

if 20/20 or better preoperatively c~ (0.0, 5.8) (0.0, 3.8) (0.0, 3.8) (0.0, 3.9)

BSCVA = Best Spectacle Corrected Visual Acuity Cl = 95% Confidence Interval D = Diopter

Page 34 of 52 7260-0107 Rev. A


Table 24. Summary of Key Safety Parameters at 3 and 6 MonthsStratified by Diopter (D) of Preoperative Cycloplegic Cylinder

_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ S~M ONT HS.. _ _ _ _ _ _ _ _

-1.00 to -2.00 to -3.00 to -4.00 to -5.00 toSafety Parameters -1.99 -2.99 -3.99 -6.00 Total

Loss of > 2 Lines BSCVA n/N 0/24 0/37 0/25 0/17 0/7 0/110__________________________ % 0.0% 0.0% 0.0% 0.0% 0.0% 0.0%

Loss of 2 Lines BSCVA /N 0/24 0/37 0/25 0/17 0/7 0/110% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0%n/N 0/24 0/37 0/25 0/17 0/7 0/110% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0%

n/N 0/24 0/37 0/25 0/17 0/7 0/110% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0%

BSCVA worse than 20/25 n/N 0/22 0/36 0/23 0/9 0/4 0/94if 20/20 or better preoperatively % 0.0% 0.0% 0.0% 0.0% 0.0%

6 MONTHS

Safety Parameters -1.00 to -2.00 to -3.00 to -4.00 to -5.00 to-1.99 -2.99 -3.99 -4.99 -6.00 Total

n/N 0/24 0/37 0/25 0/17 0/7 0/l10Loss of > 2 Lines BSCVA % 0.0% 0.0% 0.0% 0.0% 0.0% 0.0%

Loss of 2 Lines BSCVA n/N 0/24 0/37 0/25 0/17 0/7 0/110% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0%

BSCVA worse than 20/40 n/N 0/24 0/37 0/25 0/17 0/7 0/110% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0%

n/N 0/24 0/37 0/25 0/17 0/7 0/110% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0%

BSCVA worse than 20/25 n/N 0/22 0/36 0/23 0/9 0/4 0/94if 20/20 or better preoperatively % 0.0% 0.0% 0.0% 0.0% 0.0% 0.0%


7260-0107 Rev. A Page 35 of 52


Table 25. Summary of Key Safety Parameters at 3 and 6 MonthsStratified by Diopter (D) of Preoperative Cycloplegic Refraction Spherical Equivalent

.3 MONTHS ___ ____ _ _

-1.00 to 0.00 to +0.01 to +1.00 to-2.00 -0.99 +0.99 +2.00 Total

n/N 0/8 0/45 0/45 0/12 0/110Loss of > 2 Lines BSCVA 0.0% 0.0% 0.0% 0.0% 0.0%

Loss of2 Line BSCVAnfN 0/8 0/45 0/45 0/12 0/110% 0.0% 0.0% 0.0% 0.0% 0.0%

n/N 0/8 0/45 0/45, 0/12 0/110% 0.0% 0.0% 0.0% 0.0% 0.0%

n/N 0/8 0/45 0/45 0/12 0/110Increase> 2D cylinder magnitude % 0.0% 0.0% 0.0% 0.0% 0.0%

BSCVA worse than 20/25 nfN 0/6 0/41 0/36 0/11 0/94if20/20 or better preoperatively % 0.0% 0.0% 0.0% 0.0% 0.0%

_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _6 M O NTH S _ _ _ _ _ _ _ _ _

-1.00 to 0.00 to +0.01 to +1.00 toSafety Parameters2009 +99 +0Toa-2.00 -0.99 +0.99 Total

Loss of > 2 Lines BSCVA n/N 0/8 0/45 0/45 0/12 0/110_______ ______ _______ ______ % 0.0% 0.0% 0.0% 0.0% 0.0%


BSCVA worse than 20/40 n/N 0/8 0/45 0/45 0/12 0/110% 0.0% 0.0% 0.0% 0.0% 0.0%

n/N 0/8 0/45 0/45 0/12 0/110% 0.0% 0.0% 0.0.% 0.0%



Page 36 of 52 7260-0107 Rev A


b) Change in Best Spectacle Corrected Visual Acuity

Using a standard (high-contrast) visual acuity chart, BSCVA was measured under dim roomillumination (10-12 cd/m2). At least 90.9% of eyes had a gain or no change in BSCVA frompreoperative at all postoperative intervals (Table 26). A trend for postoperative BSCVA gain ofI line was observed compared to a loss of I line at 3 months (39.1% vs. 6.4%) and at 6 months(38.2% vs. 3.6%). While a small percentage of eyes had a BSCVA gain of 2 lines at 3 months(0.9%) and at 6 months (3.6%), no eyes had a BSCVA loss of 2 lines at 3 months or later.

Table 26. Change in Best Spectacle Corrected Visual Acuity

I MONTH 3MoNTHS 6Mo mS M940fhn/N 0/110 0/110 0/110 0/108

Decrease > 2 Lines % 0.0% 0.0% 0.0% 0.0%

n/N 1/110 0/110 0/110 0/108% 0.9% 0.0% 0.0% 0.0%

n/N 9/110 7/110 4/110 6/108DcesI e% 8.2% 6.4% j 3.6% 5.6%n/N 68/110 59/110 60/110 51/108% 61.8% 53.6% 54.5% 47.2%

Increase I Line n/N 29/110 43/110 42/110 48/108% 26.4% 39.1% 38.2% 44.4%

Increase 2 Lines n/N 3/110 1/110 [ 4/110 3/108% 2.7% 0.9% 3.6% 2.8%

n/N 0/110 0/110 0/110 0/108Increase > 2 Lines %00 .%00%0.0% I 0.0% 0.0% 0.0%

Low contrast BSCVA was measured using a 10% low contrast visual acuity chart under dimroom illumination (Table 27). Slightly more eyes had a gain than loss of I line of low contrastBSCVA at 3 months (30.6% vs. 17.6%) and at 6 months (33.6% vs. 19.1%). In addition, moreeyes had a gain than loss ofŽ> 2 lines of low contrast BSCVA at 3 months (7.4% vs. 4.6%) and6 months (8.2% vs. 2.7%).

Table 27. Change in Low Contrast Best Spectacle Corrected Visual Acuity

3 MONTHS 6 MONTHSn/N 1/108 I 0/110

Decrease > 2 Lines 0.9% 0.0%

Decrease 2 Lines n/N 4/108 3/110% 3.7% 2.7%

Decrease I Line n/N 19/108 21/110% 17.6% 19.1%

n/N 43/108 40/I 10% 39.8% 36.4%

n/N 33/108 37/110Increase I Line3063.%

n/N I7/108 8/110Increase 2 Lines % 7.10 7.3%% 6.5% 7.3%

n/N 1/108 1/110Increase > 2 Lines

% ~~~~0.9% 0.9%

7260-0107 Rev. A Page 37 of 52


8. Change in Contrast Sensitivity

Contrast sensitivity was measured under both photopic and mesopic conditions using theCSV-1000 (VectorVision 9). A clinically significant change from preoperative level was definedas > 2 levels (> 0.3 log units) at two or more spatial frequencies (Table 28).

The majority of eyes did not have a clinically significant change in contrast sensitivity frompreoperative to postoperative. Of the eyes with a change in photopic contrast sensitivity, slightlyfewer eyes showed a gain than loss at 3 months (2.7% vs. 6.4%) and an equal percentage of eyes(5.5%) had a gain or loss at 6 months. Under mesopic conditions, a trend for more eyes with again than loss of contrast sensitivity was observed at 3 months (22.4% vs. 11.2%) and at6 months (26.2% vs. 10.3%).

In addition, a gain from preoperative was observed in the mean contrast sensitivity log at eachspatial frequency under photopic and mesopic conditions at 3 and 6 months (Table 29). Whileno statistically significant change was observed at 3 months, statistically significant gains(p<0.05) were noted at 6 cycles per degree (cpd) under photopic conditions and for all spatialfrequencies under mesopic conditions at 6 months.

Table 28. Change of > 2 Levels (> 0.3 Log) at 2 or More Spatial Frequencies

Photopic Mesopic*3 MoNTHS 6 MONTHS 3 MONTHS 6 MONTHS

n/N 7/110 6/110 12/107 11/107% 6.4% 5.5% 11.2% 10.3%

n/N 100/110 98/1 10 71/107 68/107% 90.9% 89.1% 66.4% 63.6%

Gain n/N 3/110 6/110 24/107 28/107% 2.7% 5.5% 22.4% 26.2%

Table 29. Comparison of Mean Contrast Sensitivity Log by Spatial Frequency

Spatial Preop 3-Month 6-MonthFrequency (cpd) Mean + SD Mean ± SD Mean + SD p-valuet

Photopic (N=1 10) (N=110) (N=1 10)3 1.73 ±0.15 1.75 ±0.19 0.156 1.75 ± 0.17 0.1156 1.92 ± 0.19 1.94 ± 0.25 0.204 1.96 ± 0.22 0.018

12 1.56 ± 0.25 1.56 ± 0.28 0.986 1.57 A± 0.31 0.748

18 1.09 ± 0.26 1.08 ± 0.31 0.764 1.08 ± 0.32 0.892

Mesopic* (N=107) (N=107) (N=107)1.51 +0.23 1.55 + 0.26 0.134 1.56 · 0.24 0.036

6 1.48 + 0.25 1.52 ± 0.28 0.238 1.56 ± 0.27 0.009

12 0.91 ±0.32 0.98 ± 0.31 0.086 1.00 ± 0.33 0.04818 0.41 ±0.34 0.42 ± 0.36 0.749 0.50 ± 0.36 0.016

'Mesopic illumination with neutral density filters in front of eyest p-value from paired t-test of differences between preoperative and postoperative means;p < 0.05 is statistically significant, shown in bold

Iector Vision TM of Brain Lab AGPage 38 of 52 7260-0107 Rev. A

[Ut


9. Patient Questionnaire

Patients were asked to rate symptoms without glasses or contact lenses after surgery as comparedto their recollection of symptoms before surgery, as shown in Table 30. The symptoms reportedas "worse" or "significantly worse" in >10% of eyes at 6 months were dryness, light sensitivity,blurring of vision, fluctuation of vision, glare, halos, and night driving difficulty.

Table 30. Postoperative Change in Subjective Symptoms without Correctionvs. Preoperative*3 MONTHS (N 1!0)

Significantly No · SignificantlyComfort Symptoms Better Change Worse

Burning 0.0% 10.0% 86.4% 2.7% 0.9%Dryness 3.6% 7.3% 47.3% 40.0% 1.8%Excessive Tearing 1.8% 2.7% 95.5% 0.0% 0.0%Gritty Feeling 3.6% 5.5% 83.6% 6.4% 0.9%Headache 7.3% 17.3% 70.9% 4.5% 0.0%Light Sensitivity 10.9% 7.3% 54.5% 27.3% 0.0%Pain 4.5% 5.5% 81.8% 6.4% 1.8%Redness 0.0% 11.8% 81.8% 4.5% 1.8%Visual SymptomsBlurring of Vision 14.5% 17.3% 46.4% 20.0% 1.8%Double Vision 11.8% 8.2% 71.8% 8.2% 0.0%Fluctuation of Vision 5.5% 8.2% 62.7% 20.0% 3.6%Glare 10.9% 10.0% 52.7% 26.4% 0.0%Halos 8.2% 5.5% 59.1% 27.3% 0.0%NNight Driving Difficulty 21.8% 10.0% 48.2% 20.0% 0.0%

6MONTHS(N=110) ISignificantly No Significantly

Comfort Symptoms Better Better Change Worse WorseBurning 4.5% 9.1% 79.1% 6.4% 0.9%Dryness 5.5% 6.4% 49.1% 36.4% 2.7%Excessive Tearing 2.7% 4.5% 90.0% 2.7% 0.0%Gritty Feeling 2.7% 5.5% 84.5% 6.4% 0.9%Headache 9.1% 10.0% 76.4% 4.5% 0.0%Light Sensitivity 10.9% 11.8% 54.5% 20.9% 1.8%Pain 6.4% 4.5% 84.5% 4.5% 0.0%Redness 3.6% 7.3% 81.8% 7.3% 0.0%Visual SymptomsBlurring of Vision 13.6% 15.5% 49.1% 13.6% 8.2%Double Vision 7.3% 12.7% 73.6% 4.5% 1.8%Fluctuation of Vision 8.2% 10.0% 55.5% 21.8% 4.5%Glare 10.0% 8.2% 68.2% 13.6% 0.0%Halos 10.0% 3.6% 63.6% 19.1% 3.6%Night Driving Difficult 19.1% 47.3% 10.9% 3.6%

Based on the patients' comparison of symptom severity after surgery as better or worse compared to theirrecollection of symptom severity before surgery.

7260-0107 Rev. A Page 39 of 52


Compared to preoperative, uncorrected quality of vision at 6 months was reported as better orsignificantly better in 86.3% of eyes, same in 4.5% and worse or significantly worse in 9.1%(Table 31). Satisfaction with surgery at 6 months was reported as satisfied or extremely satisfiedin 73.7% of eyes, unsure in 10.9%, and unsatisfied or extremely unsatisfied in 15.4% (Table 32).Frequency of wearing distance correction at 6 months was reported as never in 81.8% of eyesand at least some of the time in 18.2% with frequent or constant use in 11.8% (Table 33).

Table 31. Postoperative Quality of Vision without Correctionvs. Preoperative*

3MONTHS 6 MoITMS_ _ _ _ _ _ _ _ _ _ _ _ _ _( N = 0 8) N 1 0

Significantly Better 54.6% 52.7%Better 28.7% 33.6%Same 7.4% 4.5%Worse 7.4% 5.5%Significantly Worse 1.9% 3.6%

* Based on the patients' comparison of quality of vision after surgery as better or worsecompared to their recollection of quality of vision before surgery.

Table 32. Postoperative Satisfaction with Surgery

3 MONTHS 6 MONTHS(N=108) (N=l10)

Extremely Satisfied 47.2% 48.2%Satisfied 26.9% 25.5%Not Sure 15.7% 10.9%Unsatisfied 6.5% 11.8%Extremely Unsatisfied 3.7% 3.6%

Table 33. Postoperative Frequency of Distance Correction

3 MONTHS 6 MONTHS(N=108) (N=l 10)

Never 85.2% 81.8%Seldom 3.7% 6.4%Frequently 1.9% 1.8%Constantly 9.3% 10.0%

10. Retreatment

There are insufficient data for retreatment to establish safety and effectiveness.

Page 40 of 52 7260-0107 Rev. A


11. Statistical Analysis Outcomes

Statistical analysis was performed to assess for potential associations between demographic andbaseline characteristics and clinical outcomes. Age, gender, race, preoperative cycloplegic cylinder,preoperative CRSE, operative room humidity and temperature were the characteristics considered tohave the most potential for clinical relevance to the procedure. Outcomes evaluated at refractivestability (3 months) and at 6 months included: BSCVA loss of> 2 lines; UCVA of 20/20 or betterand 20/40 or better; and accuracy of MRSE, manifest sphere and manifest cylinder magnitude within0.50D and 1.000 of emmetropia.One-sided exact binomial tests (c=0.05) were used to support the observed overall rates of safety andeffectiveness outcomes to the FDA Guidance Document targets. There was no BSCVA loss of> 2 lines at 3 and 6 months, thereby meeting the FDA target rate of < 5% of eyes with BSCVA lossof > 2 lines for safety. FDA targets were met or exceeded for effectiveness outcomes overall,including UCVA 20/40 or better and accuracy of MRSE within 0.50D and within 1.00D ofemmetropia. For each baseline subgroup, the observed rate either met the target or the 95%confidence interval (CI) contained the FDA target.

To assess the consistency of outcomes across characteristics, differences in rates among subgroupswere assessed using the Cochran-Mantel-Haenszel (CMH) test. No statistical significance wasobserved among subgroups of preoperative CRSE for any outcome. Statistically significant (p<0.05)trends among subgroups are listed below by characteristic.

Among age subgroups by decade over a range of 20 to 60 years, higher rates were observed inyounger patients as compared to older patients for the following outcomes:

* UCVA 20/20 or better at 3 months (p=0. 0 129). The observed rate was > 60.0% for subgroupsbetween 20 to 49 years vs. 33.3% for 50 to 60 years. At 6 months, no statistical significance remainedamong age subgroups for UCVA 20/20 or better.

* UCVA of 20/40 or better at 3 months (p-0.0020). The observed rate was 100% for subgroupsbetween 20 to 49 years vs. 81.5% for 50 to 60 years, although the 95% CI contained the FDA targetof 85%. At 6 months, no statistical significance by age remained and all age subgroups exceeded theFDA target for UCVA of 20/40 or better.

• MRSE within 0.50D at 3 and 6 months (p=0.01 14 and p-0.0056). The observed rate was > 76.2% at3 and 6 months for subgroups between 20 to 49 years vs. 40.7% at 3 months and 51.9% at 6 monthsfor 50 to 60 years with the FDA target of 50% included in the 95% Cl. All age subgroups met orexceeded the FDA target for MRSE within 0.50D at 6 months.

* No statistical significance by age was observed for accuracy of MRSE within 1.00D and all agesubgroups met or exceeded the FDA target for MRSE within 1.00D at 3 and 6 months. However,older patients, primarily between 40 and 60 years, were more likely to have a hyperopic MRSE ofmore than +1.00D at 3 and 6 months (p-0.0108 and pO0.0013). Younger patients were more likely tohave a myopic MRSE of more than -l.00D at 3 and 6 months (p-0.0391), which was observed in twoeyes of a 20 year-old patient.

* Manifest sphere within 0.50D at 3 and 6 months (p-0.0005 and p-0.0 027). The observed rate wasŽ 71.4% for subgroups between 20 to 49 years vs. 37.0% for 50 to 60 years.

· Manifest sphere within 1.00D at 6 months (p=0.0005). The observed rate was > 91.4% for subgroupsbetween 20 to 49 years vs. 66.7% for 50 to 60 years. Older patients, primarily between 40 and60 years, were more likely to have a hyperopic manifest sphere of more than +1.00D at 3 and6 months (p-0.00 42 and p=0.0005). Younger patients were more likely to have a myopic manifestsphere of more than -1.00D at 3 months (p-0.039 1), which was observed in two eyes of a 20 year-oldpatient.

7260-0107 Rev. A Page 41 of52


Preoperative astigmatism measured in subgroups by diopter of cycloplegic cylinder over a range from -1.00D to -6.00D. Eyes with lower preoperative astigmatism showed higher rates as compared to eyeswith higher preoperative astigmatism for the following outcomes (observed rates at 3 and 6 monthsby preoperative cycloplegic cylinder are shown in Table 6):

* UCVA 20/20 or better at 3 and 6 months (p=0.0404 and p=0.0060). All preoperative cylindersubgroups met or exceeded the FDA target for UCVA of 20/40 or better at 3 and 6 months.

* MRSE within 0.50D at 3 and 6 months (p=0.0038 and p=0.0011). All preoperative cylindersubgroups met or exceeded the FDA target for MRSE within 0.50D at 3 and 6 months.

* MRSE within 1.000 at 3 and 6 months (p=0.0304 and p=0.0433). All preoperative cylindersubgroups met or exceeded the FDA target for MRSE within 1.000 at 3.and 6 months.

* Manifest sphere within I.00D at 3 months (p=0.0082). No statistical significance based onpreoperative cylinder remained for manifest sphere at 6 months. In addition, eyes with higherpreoperative astigmatism were more likely to have a hyperopic manifest sphere of more than +ID.00at 3 months compared to eyes with lower preoperative astigmatism (p=0.0412).

* Manifest cylinder magnitude < 0.50D at 3 months (p=0.0227).

* Manifest cylinder magnitude < 1.00D at 3 and 6 months (p-0.0002 and p=0.0012).

Race was analyzed in two subgroups, 94.5% Caucasians and 5.5% other races, including Hispanic(3.6%) and Indian (1.8%). Note that apparent associations by race should be interpreted with cautionbecause of the small sample size of six eyes in the other races subgroup. Caucasians had higher ratesthan other races for the following outcomes:

* MRSE within 0.50D at 3 months (p=O.O380). The observed rate was 73.1% for Caucasians vs. two ofsix eyes (33.3%) in the other races subgroup, although the 95% CI contained the FDA target of 50%.At 6 months, no statistically significant difference remained by race for MRSE within 0.50D. Bothsubgroups met or exceeded the FDA target for MRSE within 0.50D at 6 months and for MRSE within1.00D at 3 and 6 months.

* Manifest sphere within 0.50D at 6 months (p-0.0380). The observed rate was 73.1% for Caucasiansvs. two of six eyes (33.3%) in the other races subgroup.

* Manifest cylinder magnitude < 1.OOD at 3 months (p=0.0345). The observed rate was 92.3% forCaucasians vs. four of six eyes (66.7%) in the other races subgroup. At 6 months, no statisticallysignificant difference based on race remained for manifest cylinder outcomes.

Room temperature, room humidity and gender each had one statistically significant association withpostoperative manifest sphere or manifest cylinder magnitude, as follows:

* Eyes treated in a room with a lower temperature between 65.0°F and 69.9°F showed higher rates thaneyes treated in a room between 70.0°F and 74.9°F for manifest sphere within 1.00D at 3 months(97.0% vs. 83.1%; p-0.0467).

* Eyes treated in a lower room humidity showed higher rates as compared to eyes treated in higherroom humidity for manifest cylinder magnitude < 1.00D at 6 months (p-0.0 450). The observed ratewas > 81.3% for room humidity subgroups between 18% to 59% vs. 0.0% for the two eyes of onepatient treated in a room humidity of 63%.

* Females showed higher rates as compared to males for manifest cylinder magnitude <1.00D at3 months (96.6% vs. 84.3%; p-0.0 260) and at 6 months (96.6% vs. 80.4%; p=0.006 8).

Page 42 of 52 7260-0107 Rev A

CustomCormea® LASIK Physician's Booklet - Mixed Astigmatism

12. Comparative Analysis by Defocus Type

To optimize the CustomCornea® wavefront-guided LASIK treatment of mixed astigmatism, eyeswere categorized as myopic or hyperopic based on the preoperative wavefront defocus error. Myopicor hyperopic components of the algorithm were used as determined by the preoperative wavefrontdefocus. The study included 85 eyes with a myopic defocus and 25 eyes with a hyperopic defocusbased on the preoperative wavefront.

Clinical outcomes at 3 and 6 months for each preoperative wavefront defocus type were compared toestablished target rates for refractive surgery. In addition, outcomes were compared between myopicand hyperopic defocus types. Outcomes evaluated at refractive stability (3 months) and at 6 monthsincluded: BSCVA loss of > 2 lines; UCVA of 20/20 or better and 20/40 or better; and accuracy ofMRSE, manifest sphere and manifest cylinder magnitude within 0.50D and 1.00D of emmetropia.Postoperative outcomes of myopia or hyperopia of more than 1.00D by MRSE and manifest spherewere also evaluated.

One-sided exact binomial tests (a=0.05) were used to compare the observed overall rates of eyesmeeting safety and effectiveness criteria to the FDA Guidance Document target rates. There was noBSCVA loss ofŽ> 2 lines at 3 and 6 months for both subgroups, thereby meeting the FDA target rateof < 5% of eyes with BSCVA loss of > 2 lines for safety. Both defocus types of mixed astigmaticeyes exceeded FDA targets overall for effectiveness including for UCVA of 20/40 or better andaccuracy of MRSE within 0.50D and 1.00D of emmetropia at 3 and 6 months.

To compare clinical outcomes of mixed astigmatic eyes by preoperative defocus type, the Cochran-Mantel-Haenszel (CMH) test was used to assess for differences. A p-value < 0.05 would indicate astatistically significant difference in outcomes between defocus types. Myopic and hyperopicdefocus groups had outcomes that were not significantly different. Tables 34 and 35 display thecomparative analysis by defocus type at 3 and 6 months.

7260-0107 Rev A Page 43 of 52



Criteria CMH Myopic Hyperopic FDA TargetCriteria C MH P-Value' Defocus Defecus P-Value"


UCVA 20/20 or better 0.6183 % 57.6% 52.0% 56.4% --

CI (46.4,68.3) (31.3, 72.2) (46.6,65.8)n/N 80/85 25/25 105/110 Ž85%

UCVA 20/40 or better 0.2166 % 94.1% 100.0% 95.5% 0Cl (86.8,98.1) (86.3, 100.0) (89.7,98.5)n/N 61/85 17/25 78/110

MRSE ± 0.50D 0.7169 % 71.8% 68.0% 70.9% 50%_ICI (61.0, 81.0) (46.5,85.1) (61.0000n/N 79/85 23/25 102/110

MRSE ± 1.00D 0.8740 % 2.9%92.0% 92.7% > _ 75%Cl (85.3,997.4) (74.0, 99.0) (86.2, 96.8)

Accuracy of Manifest Sphere and Cylindern/N 57/85 22/25 79/110

Manifest Sphere ± 0.50D 0.0417 % 67.1% 88.0% 71.8% -

CI (56.0, 76.9) (68.8, 97.5) (62.4, 80.0)n/N 74/85 22/25 96/110

Manifest Sphere ± 1.00D 0.9017 % 87.1% 88.0% 87.3% --

CI (78.0, 93.4) (68.8, 97.5) (79.6, 92.9)Manifest Cylinder Magnitude n/N 55/85 18/25 73/110

<ai5sD 0.4994 % 64.7% 72.0% 66.4% --<0.50D __________________ Cl (53.6, 74.8) (50.6, 87.9) (56.7, 75.1)

Manifest Cylinder Magnitude n/N 79/85 21/25 100/110Man1feOD CylinderMagnitude 0.1736 % 92.9% 84.0% 90.9% -

< _______________________ _D_______ Cl (85.3, 97.4) (63.9, 95.5) (83.9, 95.6)Postoperative Manifest Spherical Equivalent and Manifest Sphere

Postoperative MRSE nfN 6/85 0/25 6/110> +1.OOD (Hyperopic) 0.1738 % 7.1% 0.0% 5.5%

Cl (2.6, 14.7) (0.0, 13.7) (2.0, 11.5)n/N 0/85 2/25 2/110

Postoperativ (MRSE 0.0088 % 0.0% 8.0% 1.8%CI (0.0, 4.2) (1.0, 26.0) (0.2, 6.4)

n/N 11/85 1/25 12/I 10Postoperative Manifest Sphere 0.2095 % 12.9% 4.05 10> +I.00D (Hyperopic) % 1.%40 09

CI (6.6, 22.0) (0.1, 20.4) (5.8, 18.3)n/N 0/85 2/25 2/110Postoperative Manifest Sphere 08 0.0% 820% 1 -

< -1.0D (Mopic)0.0088 % 0.0% 8.0% 1.8%Cl (0.0, 4.2) (1.0, 26.0) (0.2, 6.4)

Cochran-Mantel-Haenszel (CMH) Test with rank scores** One-sided exact binomial test comparison to the FDA targetCl = 95% Confidence Interval p < 0.05 is statistically significantUCVA = Uncorrected Visual Acuity MRSE = Manifest Refraction Spherical EquivalentD = Diopter BSCVA = Best Spectacle Corrected Visual Acuity

Page 44 of 52 7260-0107 Rev. A

14o3



Criteria CMH Myopic Hyperopic Total FDA Targeti P-Value Defocus Defocus P-Value"


UCVA 20/20 or better 0.3687 % 65.9% 56.0% 63.6% --

Cl (54.8, 75.8) (34.9, 75.6) (53.9, 72.6)n/N 83/85 25/25 108/110

UCVA 20/40 or better 0.4410 % 97.6% 100.0% 98.2% Ž85%C1 (91.8, 99.7) (86.3, 100.0) (93.6, 99.8)n/N 64/85 20/25 84/110

MRSE ± 0.50D 0.6279 % 75.3% 80.0% 76.4% 50%Cl (64.7, 84.0) (59.3, 93.2) (67.3, 83.9)n/N 77/85 23/25 100/110

MRSE ± 1.000 0.8299 % 90.6% 92.0% 90.9% Ž75%Cl (82.3, 95.8) (74.0, 99.0) (83.9, 95.6)

Accuracy of Manifest Sphere and Cylindern/N 59/85 19/25 78/110

Manifest Sphere ± 0.50D 0.5257 % 69.4% 76.0% 70.9% --

CI (58.5, 79.0) (54.9,90.6) (61.5, 79.2)n/N 73/85 24/25 97/1 10

Manifest Sphere + 1.00D 0.1703 % 85.9% 96.0% 88.2% -

Cl (76.6, 92.5) (79.6, 99.9) (80.6, 93.6)n/N 55/85 16/25 71/110

Manifest Cylinder Magnitude 0.9485 % 64.7% 64.0% 64.5% --

< 0.500 CI (53.6, 74,8) (42.5, 82.0) (54.9, 73.4)

Manifest Cylinder Magnitude n/N 78/85 20/25 98/110Manifest CylinderMagnitue 00987 % 91.8% 80.0% 89.1% --

C1 (83.8, 96.6) (59.3, 93.2) (81.7, 94.2)Postoperative Manifest Spherical Equivalent and Manifest Sphere

Postoperative MRSE n/N 8/85 0/25 8/1100.1128 % 9.4% 0.0% 7.3% --

CI (4.2, 17.7) (0.0, 13.7) (3.2, 13.8)Postoperative MRSE n/N 0/85 2/25 2/110

< (Mopi)0.0088 % 0.0% 8.0% 1.8% --

CI (0.0, 4.2) (1.0, 26.0) (0.2, 6.4)n/N 12/85 1/25 13/1 10Postoperative Manifest Sphere 073 12/85 1.05 1110

> +I.OD (yperpic)0.1703 % I4.1 % 4.0% 11.8% -Cl (7.5,23.4) (0.1, 20.4) (6.4, 19.4)

Postoperative Manifest Sphere nJN 0/85 0/25 0/110NA % 0.0% ~~0.0% 0.0% --< -1.00D (Myopic) N .%/

Cl (0.0, 4.2) (0.0, 13.7) (0.0, 3.3)Cochran-Mantel-Haenszel (CMH) Test with rank scores NA = Not ApplicableOne-sided exact binomial test comparison to the FDA target

CI = 95% Confidence Interval p < 0.05 is statistically significantUCVA = Uncorrected Visual Acuity MRSE = Manifest Refraction Spherical EquivalentD = Diopter BSCVA = Best Spectacle Corrected Visual Acuity

7260-0107 Rev. A Page 45 of 52


Alcon

LAD 11'*6000'E X C I M E R L A S E R

FACTS YOU NEED TO KNOW ABOUTCustomCornea® LASER ASSISTED IN-SITU

KERATOMILEUSIS (LASIK) SURGERY

PATIENT INFORMATION BOOKLET

For Mixed Astigmatism of 1.00D to less than 5.00D cycloplegic cylinder magnitude

Please read this entire booklet. Discuss its contents with your doctor so that youhave all of your questions answered to your satisfaction. Ask any questions youmay have before you agree to the surgery.


Orlando, FL 32826 U.S.A.

Tel: (877) 523-2784Fax: (407) 384-1677www.ladarvision.com

Outside the U.S., contact your local Alcon office

7260-0106 Rev A Page 1 of 29

'/iO

CustomCornea~ LASIK Patient Information Booklet - Mixed Astigmatism

C 2006 Alcon, Inc.

This booklet may be reproduced only by a treating physician for use with patients considering CustomCornea®Laser Assisted In-Situ Keratomileusis (LASIK) Surgery using the LADAR6000Th System. All other rights reserved.


Revision Description DaE ]A DCN 10064 - original release

Page 2 of 29 7260-01 06 Rev. A


TABLE OF CONTENTS

A . IN TR O D U C T IO N ................................... ............:............................................................5

B. How DOES CUSTOMCORNEA® LASIK CORRECT MIXED ASTIGMATISM? ......................... 6

C. BENEFITS OF CUSTOMCORNEA® LASIK .............................................................. 8CLINICAL STUDY TO EVALUATE BENEFITS .................................................................... 8

Patient Demographics .......................................................................................... 8V isual A cuity M easurem ent ................................................................................... 8V isual A cuity w ithout G lasses ........................................... .................................... 9Visual Acuity without Glasses After Surgery and with Glasses Before Surgery ..... 9Patient Demographics and Surgery Outcomes .................................................... 10P atient Q uestionnaire .......................................................................................... 10

D. RISKSOFCUSTOMCORNEA®LASIK ....................................................... 2...................12CONTRAINDICATIONS -- WHEN CAN'T You HAVE SURGERY? . ....................................... 12

WHAT WARNINGS AND OTHER INFORMATION Do You NEED TO KNOW ABOUT? . . ........... 13W a rn in g s ................... .......................................................................................... 1 3P re c a u tio n s .......................................................................................................... 1 3During the First W eek Following Surgery ............................................................ 14During One to Six Months Following Surgery ...................................................... 15

CLINICAL STUDY TO EVALUATE R ISKS ......................................................................... 15V isual A cuity w ith G lasses ........................................................................... 1.......15Change in Visual Acuity with Glasses After Surgery ........................................... 16Contrast Sensitivity ....................................... ....................................................... 16Adverse Events and Complications ............... 1.....................................................17Worse and Significantly Worse Symptoms After Surgery .................................... 18

E. ARE YOU A GOOD CANDIDATE FOR CUSTOMCORNEA® LASIK? ................................... 19

F. WHAT SHOULD You EXPECT DURING CUSTOMCORNEA® LASIK SURGERY? ................. 19BEFORE THE SURGERY ..................................................... I9.....................................19

T H E D AY O F S U R G ER Y ..............................................................................................19

THE FIRST DAYS AFTER SURGERY ...................... ...................................................... 20

G . QUESTIONS TO ASK YOUR D OCTOR ............................................................................ 21

H. SELF-TEST .... ............................................................................. 22........................22

I. SUMMARY OF IMPORTANT INFORMATION ..................................................................... 23

J. GLOSSARY..............................................................................2.................4......24

K. PATIENT ASSISTANCE INFORMATION ......................... ........................ ...... 27

L . IN D E X ................ ............ ........... ......................................... -8.......................2 8

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Page 4 of 29 7260-0106 Rev A

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A. Introduction

The purpose of this booklet is to provide you with information on laser eye surgery. Please readthis entire booklet carefully. See the "Glossary" (Section J) for an explanation of words shown initalics. Discuss your questions with a doctor trained in laser eye surgery. You need tounderstand the benefits and risks of this surgery before making a decision to have surgery.

Mixed astigmatism is a condition that causes blurred distant and near vision because the eye isboth nearsighted and farsighted. If you have mixed astigmatism, you may have difficulty seeingclearly at distance and near. Glasses, contact lenses, or eye surgery can correct mixedastigmatism to help you see more clearly.

Laser Assisted In-Situ Keratomileusis (LASIK) is a type of eye surgery available to correctmixed astigmatism. Other eye surgeries that may be an option to correct vision are AutomatedLamnellar Keratoplasty (ALK) and Radial Keratotomy (RK). These surgeries may not meet thevision requirements for some careers, such as military service.

LASIK surgery can help you see more clearly by changing the shape of the cornea, the clearfront surface of your eye. LASIK surgery uses an excimer laser to remove tissue to reshape thecornea. An instrument called a nuicrokerazome first cuts a thin flap of tissue from the front ofyour cornea. This corneal flap is folded back, and the laser removes tissue under the flap tochange the shape of the cornea. Then the flap is put back in place for the eye to heal.

Your eyeglass prescription is the usual way to tell how much mixed astigmatism you have.Another way is to measure the shape of the wvavefroni of reflected light coming out of your eye.A wavefiront measurement gives more information about your mixed astigmatism than aneyeg-lass prescription. A wavefiront measures all of the focusing errors in your eye, includingcomplex errors that eveglasses cannot correct. These complex focusing errors are called "higher-order aberrations.

Your doctor can use either your eyeglass prescription or a wavefront measurement to planLASIK surgery. LASIK surgery based on the eyeglass prescription is called ConventionalLASIK. LASIK surgery based on the wavefront is called wavefront-guided LASIK.CustomnCornea®o LASI1K is wavefront-guided surgery with the LADAR6000 Tm Excimer LaserSystem or the LADARVision®4000 System. The LADARVision®4000 System andLADAR6000 TM System have comparable functions. Clinical studies done with theLADARVision®4000 System are applicable to the LADAR6000 TM System.

LASIK surgery is permanent. You can have LASIK surgery on one eye at a time. The secondeye may have suirgery on the same day or later, depending upon your choice and your doctor'sadvice. Discuss with your doctor whether you1 are a good candidate for CustIomCornea®~ LAS IKsurgery.

7260-0106 Rev. A Page 5 of 29

fLu


B. How Does CustomCornea® LASIK Correct Mixed Astigmatism?

You see objects because your eye focuses light into images. Your eye works like a camera. Thecamera lens focuses light to form clear images on film. Both the cornea and lens in the eye focuslight on the retina, the back surface of your eye. Diagram I shows that distant vision is clearwhen light focuses correctly.

DIAGRAM 1: NORMAL EYE

RETINA ~~~~~~~~~~~~Light fdcuses on the retina.Vision is clear.

A N ORMAL EYE

Astigmatism is a focusing error that results in blurred distant and near vision. The cornea ismore curved in some directions than others causing light to focus at different points from theretina. Vision is blurred because light does not focus correctly on the retina. When light focusesat a point in front of the retina, the eye is nearsighted. When light focuses at a point behind theretina, the eye is farsighted. An eye with mixed astigmatism is both nearsighted and farsighted.Diagram 2 shows how light focusing at different points from the retina causes blurred vision inan eye with mixed astigmatism.

DIAGRAM 2: EYE WITH MIXED ASTIGMATISM

Light focuses in front of andbehind the retina.

A MIXED ASTIGMATIC EYE Vision is blurred.

Wearing glasses and contact lenses help your eye focus light properly on the retina. LASIKsurgery focuses light properly by reshaping the cornea. LASIK surgery uses an excimer laser toremove a tiny amount of tissue from the cornea. This type of laser does not change any otherparts of the eye. Diagram 3 shows that distant vision is clearer after LASI K.

DIAGRAM 3: CORRECTION OF VISION AFTER LASIKCORNEA

Light focuses on the retinaRETINA--" after surgery.

kili~~~~' LENS ~~~~Vision is clear.

Page 6 of 29 7260-0 106 Rev. A


CustomCornea® LASIK uses a wavefront unique to your eye for treatment. This wavefront isused to guide the laser that reshapes the cornea to correct focusing errors. The doctor measuresthe wavefront by projecting light into your eye and measuring the reflected light that comes outof your eye.

The LADAR6000 TM System uses a very small laser beam to reshape the cornea. To correct formixed astigmatism, the cornea receives hundreds to thousands of laser pulses during LASIKsurgery. The system must place the laser pulses accurately to precisely reshape the cornea.Precise shaping of the cornea requires tracking and compensating for eye movement duringsurgery.

Your eyes are constantly making small movements. Some of these movements are involuntaryand you do not notice them. You cannot hold your eye perfectly still even if you try. TheLADAR6000Tm System tracks and adjusts for eye movement during surgery. A high-speedactive eye tracking system, called the LADARTracker® system, measures the eye position 4000times a second.

In a clinical study', eye movement during surgery using the LADARVision® System wasevaluated for 554 eyes. This study showed that:

• All eyes moved during surgery.

* The LADARTracker® system adjusted for this eye movement. The results of the -surgerywere about the same for eyes with large or small eye movements.

* Active eye tracking with the LADARTracker® system improves the accuracy of cornealshaping.

Without a system to track eye movements, any movement of the eye during surgery could moveit away from its correct position under the laser beam. Before each laser pulse, theLADARTracker® system calculates where the eye has moved since the last pulse and moves thebeam in exactly the same way, so the laser beam hits the cornea in the same place as if the eyehad not moved.

LADARVision& System PRK Myopia and Astigmatism study

7260-0106 Rev. A Page 7 of 29


C. Benefits of CustomCornea® LASIK

CustomCornea® LASIK surgery can correct between 1.00 to less than 5.00 diopters (D) of mixedastigmatism. If you have mixed astigmatism within this range, CustomCornea® LASIK surgerymay help you clearly see distant objects without eyeglasses or contact lenses.

Clinical Study to Evaluate Benefits

A clinical study using the LADARVision®4000 System was done to evaluate the benefits andrisks of CustomCornea® LASIK. The study included 110 eyes to determine benefits and risks.The study results are shown below and in "Risks of CustomCornea® LASIK" (Section D).

Patient Demographics

Table I shows the age, race, gender, and contact lens history of patients in the study.

Table 1. Demographics of 110 Eyes of 63 Study Patients

Age Race Gender Contact LensHistory

Average: 40.6 ± 10.7 years Caucasian 94.5% Female 53.6% None 64.5%Range: 20 to 60 years Hispanic 3.6% Male 46.4% Hard 2.7%

Indian 1.8% Soft 32.7%

Visual Acuity Measurement

Visual acuity is a measure of the sharpness of vision using a letter chart. Diagram 4 shows anexample of a visual acuity chart consisting of lines of letters. Each line of letters becomessmaller from top to bottom on the chart. Vision is sharper as smaller letters are correctly readfrom top to bottom. The chart is read at a distance to measure the sharpness of distant vision.Visual acuity is shown by two numbers: the first number is the distance and the second numberis the smallest line of letters read correctly. As the second number becomes smaller, the vision issharper. For example, a smaller line of letters is read correctly for a visual acuity of 20/20compared to 20/40.

DIAGRAM 4: EXAMPLE OF VISUAL ACUITY CHART

Z V E R DH V D E P

DZ N UVH P E D R

Page 8 of 29 7260 0106 Rev. A


Visual Acuity without Glasses

The clinical study evaluated visual acuity without glasses at a distance using a letter chart. Table2 shows that at least 93.5% of patients treated for mixed astigmatism saw 20/40 or better withoutglasses after surgery. Most states require that your vision be 20/40 or better if you drive withoutany glasses or contact lenses.

Table 2. Visual Acuity without Glasses

% of Eyes With: Before Surgery I Month 3 Months 6 Months 9 Months(N=10) (N=l10) (N-l10) .(N=Il0) (N=108)

20/20 or better* 1.1% 72.3% 63.8% 71.3% 69.6%

20/20 or better 0.9% 63.6% 56.4% 63.6% 61.1%

20/25 or better 3.6% 86.4% 80.9% 87.3% 84.3%

20/40 or better 35.5% 96.4% 95.5% 98.2% 93.5%

* if visual acuity was 20/20 or better with glasses or contact lenses before surgery(N-94 eyes at all visits up to 6 months; N=92 at 9 months). N is the number of eyes studied.

Visual Acuity without Glasses After Surgery and with Glasses Before Surgery

The clinical study compared visual acuity without glasses at a distance after surgery to visualacuity with glasses before surgery using a letter chart. Table 3 shows that 56.4% of patients at 3months and 60.0% at 6 months, saw as well or better without glasses after CustomCornea®surgery as with glasses before surgery.

Table 3. Visual Acuity without Glasses After Surgery Compared towith Glasses Before Surgery

I Month 3 Months 6 Months 9 Months% of Eyes With: (N=110) (N-110) (N=110) (N=108)2 lines better vision without glasses after LASIK 0.0% 0.0% 1.8% 1.9%than vision with glasses before surgery

I line better vision without glasses after LASIK 11.8% 16.4% 17.3% 18.5%than vision with glasses before surgery

same vision* without glasses after LASIK as 48.2% 40.0% 40.9% 39.8%vision itiih glasses before surgery

I line worse vision without glasses after LASIK 23.6% 19.1% 26.4% 19.4%than vision with glasses betbre surgery

2 lines worse vision without glasses after LASIK 8 11.8% 6.4% 10.2%than vision with glasses before surgery

more than 2 lines worse vision without glasses 8.2% 12.7% 7.3% 10.2%after LASIK than vision with glasses before surgery

* Same vision is within 2 or 3 letters on the same line of a visual acuity chaIrt.N is the number of eves studied.

7260-0106 Rev A Page 9 of 29


Patient Demographics and Surgery Outcomes


A visual acuity of 20/20 or better without glasses or contact lenses after surgery was morelikely in younger patients and patients with lower amounts of astigmatism before surgery. Avisual acuity of 20/40 or better without glasses or contact lenses after surgery was morelikely in younger patients.

* Reduction of farsightedness or nearsightedness to 0.50D or less after surgery was more likelyin younger patients, Caucasian patients* and patients with lower amounts of astigmatismbefore surgery. Reduction of farsightedness or nearsightedness to 1.00D or less after surgerywas more likely in patients with lower amounts of astigmatism before surgery.

* Reduction of astigmatism to 0.50D or less after surgery was more likely in patients withlower amounts of astigmatism before surgery. Reduction of astigmatism to 1.00D or lessafter surgery was more likely in females, Caucasian patients* and patients with loweramounts of astigmatism before surgery.


* A visual acuity of 20/20 or better without glasses or contact lenses after surgery was morelikely in patients with lower amounts of astigmatism before surgery.

* Reduction of farsightedness or nearsightedness to 0.50D or less after surgery was more likelin younger patients, Caucasian patients* and patients with lower amounts of astigmatismbefore surgery. Reduction of farsightedness or nearsightedness to 1.00D or less after surgerdwas more likely in younger patients and patients with lower amounts of astigmatism beforesurgery.

* Reduction of astigmatism to 1.00D or less after surgery was more likely in females andpatients with lower amounts of astigmatism before surgery.

Note that the clinical study included only 5.5% of patients of races other than Caucasian.

Patient Questionnaire

Patients in the clinical study were asked to rate the quality of vision after surgery compared totheir recollection of quality of vision before surgery. Table 4 shows that compared to beforesurgery, quality of vision without glasses or contact lenses at 6 months after surgery was reportedas better or significantly better in 86.3% of eyes. same in 4.5% and worse or significantly worsein 9.1%.

Page 10 of 29 7260-0106 Rev A


Table 4. Quality of Vision without Glasses or Contact Lenses AfterSurgery Compared to Before Surgery*

3 MONTHS 6 MONTHSN=108 N=110

Significantly Better 54.6% 52.7%

Better 28.7% 33.6%

Same 7.4% 4.5%

Worse 7.4% 5.5%

Significantly Worse 1.9% 3.6%

N is the number of eyes studied.* Based on the patients' comparison of quality of vision after surgery as better or worse compared to

their recollection of quality of vision before surgery.

Table 5 shows that satisfaction with surgery at 6 months was reported as satisfied or extremelysatisfied in 73.7% of eyes, unsure in 10.9%, and unsatisfied or extremely unsatisfied in 15.4%.

Table 5. Satisfaction with Surgery

3 MONTHS 6 MONTHSN=108 N=110

Extremely Satisfied 47.2% 48.2%

Satisfied 26.9% 25.5%

Not Sure 15.7% 10.9%

Unsatisfied 6.5% 11.8%

Extremely Unsatisfied 3.7% 3.6%N is the number of eyes studied.

Table 6 shows that frequency of wearing glasses or contact lenses for distance vision at6 months was reported as never in 81.8% of eyes and at least some of the time in 18.2% withfrequent or constant use in 1 1.8%.

Table 6. Frequency of Glasses or Contact Lens Wear for DistanceAfter Surgery

3 MONTIS 6 MONTHS

N-108 N=110Never 85.2% 81.8%

Seldom 3.7% 6.4%

Frequently 1.9% 1.8%

Constantly 9.3% 10.0%N is the number of eves studied.

7260-0106 Rev A Page 11 of 29

CustomCornea' LASIK Patient Information Booklet - Mixed Astigmatism

D. Risks of CustomCornea® LASIK

If you are not satisfied with your surgery results, your doctor may suggest another surgery. Nodata are available for CustomComea® LASIK retreatments.

IMPORTANT: You may need to wear glasses or contact lenses for some activities aftersurgery. CustomCornea® LASIK does not take away the need for reading glasses. You mayneed reading glasses after CustomCornea® LASIK even if you did not need them before.

In some cases, your best vision with glasses or contact lenses may be worse afterCustomCornea® LASIK surgery than it was before surgery.

A number of risks from LASIK surgery are related to the corneal flap rather than the lasertreatment. Some specific problems include: cutting an incomplete or irregular flap, loss of theflap, misalignment of the flap, and cutting all the way through the cornea with themicrokeratome. These problems can lead to other complications, such as infections, cataracts,and permanent scarring or deformity of the eye.

Contraindications - When Can't You Have Surgery?

If you have any of the following situations or conditions, the risk of LASIK surgery is greaterthan the benefit. You should NOT have LASIK surgery if you:

* are pregnant or nursing. These conditions may cause temporary and unpredictable changesin your cornea that may interfere with the accuracy of the measurement of your cornea beforethe LASIK procedure.

* have a collagen vascular (e.g., rheumatoid arthritis), autoiminune (e.g., lupus), orirnmunodeficiencv disease (e.g., AIDS). These conditions affect your body's ability to healand may result in inflammation or swelling of parts of the body such as muscles, joints, andblood vessels.

* show signs of keratoconus or any other condition that causes a thinning of your cornea. Thisunstable condition of the cornea makes it unsafe to do LASIK procedures on eyes with thiscondition.

* are taking medications with ocular side effects, such as isotretinoin (Accutane 2) for acnetreatment or amiodarone hydrochloride (Cordarone 3) for normalizing heart rhythm. Thesemedications mav affect the accuracy of the LASIK procedure or the way your cornea healsafter surgery. This may result in poor vision after surgery.

2. Iccutane Reg. TM of Hoffimann-La Roche Inc.(ordarone Reg, rM of Sanofi-Aventis

Page 12 of 29 7260-0106 Rev. A


What Warnings and Other Information Do You Need to Know About?

Warnings

If you have any of the following conditions, you may have LASIK if your doctor evaluates theseriousness of your condition and believes the benefit of having LASIK is greater than the risk.Discuss with your doctor if you have:

* diabetes. Diabetes may interfere with the healing of the cornea after LASIK.

* a history of herpes simplex or herpes zoster infection that has affected your eyes. LASIKmay be more risky for patients who have an active or previous herpes infection that hasaffected their eyes.

* significant dry eye that is unresponsive to treatment. LASIK may increase the dry eyecondition, which may or may not go away. This dryness may delay healing of the flap orinterfere with the surface of the eye after surgery.

* severe allergies. The medications taken for severe allergies may interfere with the ability ofthe eye to heal after LASIK.

You will need eye drops to enlarge your pupil to at least 7mm to 11mm before surgery so thetracking system can more easily follow your eye during surgery. This effect of eye drops is onlytemporary.

Precautions

If you have any of the following conditions, you should discuss this with your doctor. The safetyand effectiveness for LASIK have NOT been established in patients:

* with unstable mixed astigmatism. Eyes with unstable mixed astigmatism are unable to bemeasured correctly to determine the right amount of the vision correction to provide.

* with conditions that may interfere with the ability to properly measure the eye to determinethe right amount of vision correction, and may also affect the healing of the eye after thesurgery, such as:

- disease or corneal condition (for example, scar, infection, etc.).

- injury to the cornea where LASIK will reshape the cornea.- previous surgery on the cornea or inside the eye (for example, cataract surgery).

- prior history of surgery to correct vision (for example, LASIK surgery).

* with a cornea that is too thin for LASIK to be completed safely. A flap needs to be cut intothe cornea for the LASIK procedure. A proper flap cannot be created on a thin cornea.

* with a history of glaucoma (a condition usually associated with high eve pressure withdamage to the nerve in the eye and possible loss of vision). It is unknown whether LASIK issafe for eyes with glaucoma.

7260-0106 Rev. A Page 13 of 29


* who are taking the medication sumatripin succinate (lmitrex 4) for migraine headaches. It isunknown whether the use of this medication will interfere with the accuracy of themeasurement of your cornea prior to LASIK or the healing of the eye after LASIK.

* under 21 years of age because it is unknown if the eye has reached its adult vision refraction.This may result in measurement of the amount of correction to provide being incorrect.

* over the long term (more than 9 months).

* with mixed astigmatism less than 1.00D or for 5.00D or greater. Corrections falling outsideof the approved range have not been studied.

* for retreatment with this laser for LASIK. Retreatments have not been done enough times toallow an understanding of whether it is safe and effective.

Let your doctor know if you are taking any prescription medicines or any medications youbought without a prescription. These medications may interfere with the measurement prior toLASIK or the healing of the eye after LASIK.

The safety and effectiveness of wavefront-guided LASIK have only been established with anoptical zone of 6.5mm and a total treatment zone of 9.0mm.

Before surgery, your doctor should evaluate your pupil size under dim lighting conditions. Ifyour pupils in dim light are greater than the optical zone (> 6.5mm) proposed by your doctor,consult with your doctor about the risk that the surgery may cause negative effects on yourvision, such as glare, halos, and night driving difficulty.

Your doctor should also evaluate you for dry eyes before surgery. You may have dry eyes afterLASIK surgery even if you did not have dry eyes before surgery.

During the First Week Following Surgery

• You may feel pain, discomfort, or have a feeling that something is in your eye. It may last upto 7 days after surgery.

* Your vision may be blurry or you may become more sensitive to light as your eye heals.

* You may have temporary swelling of the front surface of your eye.

* The pressure inside your eye may increase, usually due to the use of anti-inflammatorymedication (eye drops) after surgery. Using another medication or stopping the anti-inflammatory medication can control the abnormal increase in eye pressure.

Inittex Reg TM of Glaxo Group Limited

Page 14 of 29 7260-0106 Rev A


During One to Six Months Following Surgery

* Your vision should be stable 3 months after surgery. Some patients may notice that theirvision improves or worsens. These small changes may occur up to 6 months or more aftersurgery. You should contact your doctor if you notice any change or loss of vision.

* You may become more sensitive to light. You may notice glare or have difficulty in drivingat night.

* You may experience some dryness.

Clinical Study to Evaluate Risks

In the clinical study using the LADARVision®4000 System for CustomCornea® LASIK, somepeople still needed glasses or contact lenses after surgery.

Astigmatism remained after surgery for some patients. After surgery, 9.1% of patients at3 months and 10.9% of patients at 6 months had astigmatism of more than ID and0.9% of patients at 3 and 6 months had astigmatism of more than 2D.

Farsightedness remained after surgery for some patients. After surgery, 5.5% of patients at3 months and 7.3% of patients at 6 months had more than ID of farsightedness and 0.9% ofpatients at 3 months had more than 2D of farsightedness. Older patients, primarily between 40and 60 years, were more likely to have more than ID of farsightedness at 3 and 6 months.Patients with higher amounts of astigmatism before surgery were more likely to have ID offarsightedness at 3 months after surgery.

Nearsightedness remained after surgery for some patients. At 3 and 6 months, 1.8% of patientshad more than I D of nearsightedness. Younger patients were more Ilikely to have more than IDof nearsightedness at 3 and 6 months, which was observed in both eyes of a 20 year-old patient.

Visual Acuity with Glasses

The clinical study evaluated visual acuity with glasses at a distance using a letter chart. Table 7shows that all patients in the study saw 20/25 or better with glasses before surgery and at 3months or later after surgery.

Table 7. Visual Acuity with Glasses (Best Vision)

"/o of Eyes With: Before Surgery I Month 3 Months 6 Months 9 Months(N=110) (N=l10) (N I10) (N_10 (N=108)

20/20 or better 85.5% 89.1% 89.1% 92.7% 93.5%20/25 or better 100.0% 99.1% 100.0% 100.0% 100.0%20/32 or better 100.0% 100.0% 100.0% 100.0% 100.0%


7260-0106 Rev. A Page 15 of 29


Change in Visual Acuity with Glasses After Surgery

Under dim room lighting conditions, the change in best vision with glasses after surgery wascompared to vision with glasses before surgery using a standard (high-contrast) visual acuitychart and a 10% low contrast visual acuity chart. A standard chart has black letters on a whitebackground. A 10% low contrast visual acuity chart has gray letters on a white background.Black letters are easier to see than gray letters. Low contrast visual acuity testing is a way todetermine how well patients can see in poor contrast conditions such as very dim light, rain,snow, and fog. Table 8 compares the change in vision with glasses before surgery to 3 and6 months after surgery.

Table 8. Change in Visual Acuity with Glasses After SurgeryCompared to Before Surgery

Standard Chart 10% Low Contrast Chart% of Eyes With: 3 Months 6 Months 3 Months 6 Months

(N=110) (N:l10) (N=108) (N=1I10)

loss of more than 2 lines 00% 0.0% 09% 00%

loss of 2 lines 0.0% 0.0% 3.7% 2.7%loss of I line 6.4% 3.6% 17.6% 19.1%

no change 53.6% 54.5% 39.8% 36.4%gain of I line 39.1% 38.2% 30.6% 33.6%

gain of 2 lines 0.9% 3.6% 6.5% 7.3%

gain of more than 2 lines 0.0% 0.0% 0.9% 0.9%N is the number of eyes studied.

Contrast Sensitivity

In the clinical study, contrast sensitivity was measured in daylight and in dim light to determinehow well patients can see in poor contrast conditions such as very dim light, rain, snow, and fog.The majority of subjects reported no change before and after surgery. Table 9 compares thechange in contrast sensitivity with glasses before surgery to 3 and 6 months after surgery.

Table 9. Change in Contrast Sensitivity with Glasses After SurgeryCompared to Before Surgery

Daylight Conditions Dim Light Conditions% of Eyes With: 3 Months 6 Months 3 Months 6 Months

_(N =10) (N=110) (N=107) (N==107)

Loss 6.4% 5.5% 11.2% 10.3%No change 90.9% 89.1% 66.4% 63.6%Gain 2.7% 5.5% 22.4% 26.2%

N is tile number of eves studied.

Page 16 of 29 7260-0106 Rev A

CustomCornea ®LASIK Patient Information Booklet - Mixed Astigmatism

Adverse Events and Complications

Some patients from the clinical study experienced adverse events and complications afterCustomCornea® LASIK surgery as shown in Table 10.

Table 10. Adverse Events and Complications

Greater than or equal to 1% of eyes (N=1 10) had:Irritation on the front surface of the cornea at one month or later 10.0%Cells growing under the corneal flap * 5.4%Inflammation of the cornea under the corneal flap 4.5%Problem with creation of the corneal flap * 1.8%Pain at one month or later 1.8%

Less than 1% of eyes (N=1 10) had:

Feeling of something in the eye at one month or later 0.9%Viral infection in the cornea 0.9%

N is the number of eyes studied.· One eye did not receive laser ablation after a problem with the creation of the corneal flap

and was not included in the analysis of eyes receiving laser surgery (N=1I I ).


* blockage of blood vessels in the retina;

• breakdown of the flap;

* corneal swelling;

* cells growing under the corneal flap with a loss of 2 or more lines of visual acuity withglasses;

* corneal scratch involving the treated area or outside the treated area at one month or later;· corneal cloudiness at six months or later with a loss of 2 or more lines of visual acuity with

glasses;* eye pressure more than 25 mmHg;* increase in eve pressUre of more than IO mmrmg compared to before surgery;* loss of more than 10 letters (more than 2 lines) of visual acuity with glasses at six months

or later;* poor alignment of the corneal flap; and* separation of the retina from the back of the ev e.

7260-0106 Rev. A Page 17 of 29


Worse and Significantly Worse Symptoms After Surgery

Patients who were treated for mixed astigmatism in the clinical study rated the change in thefollowing symptoms shown in Table II as worse or significantly worse after surgery withoutglasses or contact lenses compared to their recollection of symptoms before surgery. Thesymptoms reported as "worse" or "significantly worse" in >10% of eyes at 6 months weredryness, light sensitivity, blurring of vision, fluctuation of vision, glare, halos, and night drivingdifficulty.

Table 11. Worse or Significantly Worse Symptoms without Glasses AfterSurgery Compared to Before Surgery*

3 Months (N=1 10) 6 Months (N=1 10)Comfort Symptoms Worse Significantly Worse Significantly

Worse WorseBurning 2.7% 0.9% 6.4% 0.9%Dryness 40.0% 1.8% 36.4% 2.7%

Excessive Tearing 0.0% 0.0% 2.7% 0.0%

Gritty Feeling 6.4% 0.9% 6.4% 0.9%

Headache 4.5% 0.0% 4.5% 0.0%

Light Sensitivity 27.3% 0.0% 20.9% 1.8%

Pain 6.4% 1.8% 4.5% 0.0%

Redness 4.5% 1.8% 7.3% 0.0%

Visual Symptoms

Blurring of Vision 20.0% 1.8% 13.6% 8.2%

Double Vision 8.2% 0.0% 4.5% 1.8%

Fluctuation of Vision 20.0% 3.6% 21.8% 4.5%

Glare 26.4% 0.0% 13.6% 0.0%

Halos § 27.3% 0.0% 19.1% 3.6%

Night Driving Difficulty 20.0% 0.0% 10.9% 3.6%

N is the number of eyes studied.* Based on the patients' comparison of symptom severity after surgery as worse compared to their

recollection of symptom severity before surgery.§ Halos are circular flares or rings of light that may appear around a headlight or other lighted object.

Page 18 of29 7260-0106 Rev. A


E. Are You a Good Candidate For CustomCornea® LASIK?

If you are considering CustomCornea® LASIK, you must:

* be at least 21 years of age.* have a healthy eye with no eye disease or corneal condition (for example, scar or infection).* have mixed astigmatism of 1.00D to less than 5.OOD.* have stable mixed astigmatism as documented by less than or equal to 0.50D change each

year for at least one year before your eye examination before surgery.* be able to lie flat on your back.

• be able to look at a blinking fixation light during the entire surgery.* be able to have eye drops that numb your eye and enlarge your pupil.* understand the risks and benefits of CustomCornea® LASIK compared to other available

treatments for mixed astigmatism.* be willing to sign an Informed Consent Form, if provided by your doctor.

F. What Should You Expect During CustomCornea® LASIK Surgery?

Before the Surgery

Before surgery, your doctor needs to determine your complete medical and eye history and checkthe health of both your eyes. As part of this exam, your doctor will use a computer program tomap the front surface of your eye. This exam will determine if your eyes are healthy and if youare a good candidate for CustomCornea® LASIK.

WARNING: You must stop wearing any contact lenses at least 3 weeks before this eyeexamination. Failure to do this may affect surgical results.

Tell your doctor if you take any prescription and non-prescription medications or have anyallergies. Ask your doctor if you should eat or drink right before the surgery. You should alsoarrange for transportation since you must not drive right after the surgery. Your doctorwill let you know when your vision is good enough to drive again.

The Day of Surgery

To prepare for surgery, your doctor will use the wavefront system to take a picture of your eye.This helps to determine where the laser should treat your cornea. Your doctor will put eye dropsto dilate (enlarge) the pupil in your eye(s). After 30-40 minutes, your doctor will measure thewavefront unique to Nour eve to determine the amount of laser treatment you need.

7260-0106 Rev. A Page 19 of 29


Your doctor will then place numbing eye drops in the eye to be treated. Numbing drops are usedto control pain during surgery. The effects of the numbing eye drops will wear off after about45-60 minutes. Your doctor will ask you to lie on your back on the laser bed. The laser bed is aflat cushioned surface that can be moved to position you for surgery. Your doctor will instructyou to watch a blinking fixation light. Your doctor will place an instrument between youreyelids to hold them open during the surgery. A temporary shield will cover the eye that is nothaving surgery.

An instrument called the microkeratome creates a flap of tissue in the cornea. Then, your doctorwill reposition your head and activate the LADARTracker® system to track your eye movement.Your doctor will ask you to look directly at the blinking light. The laser in the LADAR6000""System will remove small amounts of tissue from your cornea. During the laser treatment, youwill hear a "clicking" sound of laser pulses. The tracking system will follow eye movements andallow the laser to continue the treatment. You will be under the laser for several minutes. Theuse of the laser will take about one minute. Overall, the surgery takes about 10 minutes.

IMPORTANT: You must continue looking at the blinking light throughout the treatment, evenif your vision begins to become cloudy during the procedure.

After the surgery is complete, your doctor will place some eye drops in your eye. Your doctormay cover your eye with a bandage contact lens to help heal the eye. For your eye protectionand comfort, your doctor may apply a patch or shield over your eye.

The First Days After Surgery

You may be mildly sensitive to light and have a feeling that something is in your eye.Sunglasses may make you more comfortable. Also, you may experience pain. Your doctor canprescribe pain medication to make you more comfortable during the first few days after thesurgery. A plastic shield may be used to protect your eye after LASIK. You will need to uselubricants, antibiotic, and anti-inflammatory medications in the first few days.

IMPORTANT: Use the lubricants and eye medications as directed by your doctor. Your resultsdepend upon you following your doctor's instructions.

WARNING: Your doctor will monitor you for any side effects if you need to use a topicalsteroid medication. Possible side effects of prolonged topical steroid use are:* ocular hypertension (an increase in the eye pressure);· glaucoma (a condition usually associated with high eye pressure that results in damage to tile

nerve in the eye and possible loss of vision);* cataract formation (an opacity or clouding of the lens inside the eye that can cause a loss of

vision).

DO NOT rub your eves for the first 3 to 5 days. Rubbing your eye may move the flap. If younotice any sudden decrease in your vision, you should contact your doctor immediately. Theflap may have moved and the doctor may need to reposition the flap.

Page 20 of 29 7260-0106 Rev. A

- I~~~~~~~~~~~~~~~t(


G. Questions to Ask Your Doctor

You may want to ask the following questions to help you decide if CustomCornea® LASIK withthe LADAR6000 Tm System is right for you:

* What are my other options to correct my mixed astigmatism?

* Will I have to limit my activities after surgery and for how long?

* What are the benefits of CustomCornea® LASIK for my amount of mixed astigmatism?

* What vision can I expect in the first few months after surgery?

* If CustomCornea® LASIK does not correct my vision, what is the possibility that my glasseswould need to be stronger than before? Could my need for glasses increase over time?

* Will I be able to wear contact lenses after LASIK ifI need them?

* How is LASIK likely to affect my need to wear glasses or contact lenses as I get older?

* Will my cornea heal differently if injured after having LASIK?

* Should I have LASIK surgery in my other eye?

* H-ow long will I have to wait before I can have surgery on my other eye?

* What vision problems might I experience if I have LASIK only on one eye?

• Do I have significant dry eye or large pupils that could produce undesirable side effects afterLASIK surgery?

Discuss the cost of surgery and follow-up care needs with your doctor. Most health insurancepolicies do not cover laser vision correction.

7260-0106 Rev. A Page 21 of 29


H. Self-Test

Are You An Informed And Educated Patient?

Take the test below to see if you can correctly answer the following questions after reading thisbooklet.

TRUE FALSE

1. LASIK surgery is risk-free. [ [

2. It does not matter if I wear my contact lenses before surgerywhen my doctor told me not to wear them. F] []

3. Since the LADAR6000 Tm System tracks my eye movements, Ido not have to fixate on the blinking light. F] El

4. After the surgery, there is a good chance that I will be lessdependent on eyeglasses or contact lenses. [] []

5. [ may need reading glasses after LASIK surgery, even if I didnot need them before. [ []

6. There is a risk that I may lose some vision after LASIK surgery. L] []

7. It does not matter if I am pregnant. [] F]8. If I have an autoimmune disease, I am still a good candidate for

LASIK surgery. [] E]

9. Significant dry eye or large pupils may produce undesirable sideeffects after LASIK surgery. E] [

You can find the answers to Self-Test at the bottom of the next page.

Page 22 of 29 7260-0106 Rev A


I. Summary of Important Information

* CustomCornea® LASIK is a permanent irreversible surgery to the cornea.

* You may need to wear glasses or contact lenses for some activities after surgery,CustomCornea® LASIK does not take away the need for reading glasses, even if you havenever worn them before.

* Your vision must be stable before CustomCornea® LASIK surgery. You must providewritten evidence that your mixed astigmatism has changed less than or equal to 0.50D eachyear for at least I year.

* Pregnant and nursing women should wait until they are not pregnant and not nursing to haveCustomCornea® LASIK surgery.

• You would not be a good candidate if you have autoimmune or collagen vascular diseases.If you have a condition that makes wound healing difficult, you would not be a goodcandidate.

* CustomCornea® LASIK surgery has some risks. Please read and understand this entirebooklet, especially the sections on Benefits and Risks before you agree to the surgery.

* Some other options to correct mixed astigmatism include glasses, contact lenses, andConventional LASIK. Other surgical options that may be used to correct vision are ALK andRK.

* ALK, RK and LASIK surgery may not meet the vision requirements of some occupations,such as military service.

• Before considering CustomCornea® LASIK surgery you should:

a. have a complete eye examination.

b. talk with at least one eye care professional about CustomCornea® LASIK, especially thepotential benefits, risks, and complications. You should discuss the time needed forhealing after CustomCornea® LASIK.

Answers to Self-Test Questions:

1. False (see Section D: Risks) 6. True (see Section D: Risks)2. False (see Section F: Before the Surgery) 7. False (see Section D: Contraindications)3. False (see Section F: The Day of Surgery) 8. False (see Section D: Contraindications)4. True (see Section C: Benefits) 9. True (see Section D: Precautions)5. True (see Section D: Risks)

7260-0106 Rev A Page 23 of 29

[q2-


J. Glossary

This section summarizes important terms used in this information booklet. Please discuss anyrelated questions with your doctor.

Aberration: focusing errors in the eye detectable by wavefront measurements. Examples aremixed astigmatism (lower-order) and complex errors (higher-order).

Antibiotic Medication: a drug used to treat or prevent infection. Your doctor may prescribe thismedication after LASIK surgery.

Anti-inflammatory Medication: a drug that reduces inflammation or the body's reaction toinjury or disease. Any eye surgery can cause inflammation. Your doctor may prescribe thismedication after LASIK surgery.

Astigmatism: a focusing error that results in blurred distant and near vision. The cornea is morecurved in some directions than others causing light to focus at different points from the retina.Vision is blurred because light does not focus correctly on the retina. Types of astigmatisminclude nearsighted, farsighted and mixed.

Autoimmune Disease: a condition in which the body attacks itself and results in inflammationor swelling of parts of the body, such as muscles, joints, and blood vessels. An example is lupus.If you have this type of condition, you should not have LASIK surgery.

Automated Lameliar Keratoplasty (ALK): a type of eye surgery that changes the shape of thefront surface of the eye using a microkeratome. A flap is created and tissue is removed under theflap with the microkeratome. Then the flap is put back on the eye.

Bandage Contact Lens: a soft contact lens placed on the cornea after surgery to cover the areathat was treated with the laser.

Cataract: an opacity, or clouding, of the lens inside the eye that can blur vision.

Collagen Vascular Disease: a condition that may result in inflammation or swelling of parts ofthe body, such as muscles, joints, and blood vessels. An example is rheumatoid arthritis. If youhave this type of condition, you should not have LASIK surgery.

Contraindications: any special condition that results in the treatment not being recommended.

Contrast Sensitivity: a measure of the ability of the eye to detect small lightness differencesbetween objects and the background in daylight and in dim light. For example, black lines on agray background are easier to see than gray lines on a gray background. Objects in daylight arealso easier to see than in dim light. Contrast sensitivity testing is a way to determine how wellpatients can see in poor contrast conditions such as very dim light, rain, snow, and fog.

Conventional LASIK: LASIK surgery that uses an eyeglass prescription to plan the surgery.

Cornea: the clear front layer of the eye. LASIK surgery reshapes the front surface of the corneato improve distant vision.

Corneal Flap: a thin slice of tissue on the surface of the cornea made with a microkeratome atthe beginning of the LASIK procedure. This flap is folded back before the laser shapes the innerlavers of the cornea.

Page 24 of 29 7260-0106 Rev. A


Corneal Swelling: abnormal fluid build-up in the cornea. This condition is usually temporarywith no significant effect on vision.

CustomCornea® LASIK: LASIK surgery that uses the wavefront to plan the surgery with theLADAR6000 Tm System.

Diopter: a unit of focusing power, used to describe the amount of mixed astigmatism,farsightedness or nearsightedness in an eye. Abbreviated as "D".

Excimer Laser: a form of light energy used in Conventional and CustomCornea® LASIK toremove tissue from the cornea.

Farsightedness: a focusing error that results in blurred vision that is usually worse at near thanat distance. The cornea and lens focus light at a point behind the retina resulting in blurredimages. Farsightedness is also called hyperopia.

Focusing Error: a condition in which the eye forms a blurred image on the retina. Examplesare mixed astigmatism, farsightedness, nearsightedness and higher-order aberrations (complexfocusing errors).

Glaucoma: an eye disease usually associated with high eye pressure. Glaucoma damages theoptic nerve of the eye and usually causes a progressive loss of vision.

Halos: circular flares or rings of light that may appear around a headlight or other lighted object.This symptom may occur before or after surgery.

Herpes Simplex: a type of viral infection that can recur. This virus typically causes cold soresand/or vesicles to appear on the face or other parts of the body. You should discuss any historyof this condition with your doctor before having LASIK surgery.

Herpes Zoster: a type of viral infection that can recur. This condition is a reactivation of thechicken pox virus as an adult. Vesicles appear on only one side of the body. You should discussany history of this condition with your doctor before having LASIK surgery.

Immunodeficiency Disease: a condition that compromises the body's ability to heal. Anexample is acquired immunodeficiency syndrome (AIDS). If you have this type of condition,you should not have LASIK surgery.

Inflammation: the body's reaction to injury or disease. Eye surgery can also causeinflammation.

Keratoconus: a condition of the cornea that results in a change in the shape of the cornea withthinning. If you have this condition, you should not have LASIK surgery.

Laser Assisted In-Situ Keratomileusis (LASIK): a type of eye surgery that uses amicrokeratome and a laset to improve vision. The microkeratome creates a thin, hinged flap oftissue on the cornea that is folded back. The laser shapes the tissue under the flap and the flap isput back on the eve so the tissue heals.

Lens: a structure inside the eye that helps to focus light onto the back surface (retina) of the eye.

7260-0106 Rev A Page 25 of 29


Low Contrast Visual Acuity: a measure of the sharpness of vision using a 10% low contrastchart with gray letters on a white background. Low contrast acuity testing is another way todetermine how well patients can see in poor contrast conditions such as very dim light, rain,snow, and fog.

Microkeratome: a surgical instrument used in LASIK to cut a thin flap of tissue from the frontsurface of the eye before the laser treatment is applied.

Mixed Astigmatism: a focusing error that results in blurred distant and near vision. An eye withmixed astigmatism is both nearsighted and farsighted. The cornea is more curved in somedirections than others causing light to focus at different points in front of and behind the retina.Vision is blurred because light does not focus correctly on the retina. '

Nearsightedness: a focusing error that results in blurred vision that is usually worse at distancethan at near. The cornea and lens focus light at a point in front of the retina resulting in blurredimages. Nearsightedness is also called myopia.

Ocular Hypertension: increased eye pressure.

Radial Keratotomy (RK): a type of surgery that changes the shape of the front surface of theeye by creating cuts with a blade.

Retina: the layer of nerve tissue at the back of the eye that captures images, similar to film in acamera, and sends information about those images to the brain. Light must be focused correctlyon the retina to form clear images.

Steroid Medication: a drug that reduces inflammation or the body's reaction to injury ordisease. Your doctor may prescribe this medication after LASIK surgery for a short time tomodify the healing of your eye. If you are taking this medication for a disease condition, youshould not have LASIK surgery.

Visual Acuity: a measure of the sharpness of vision using a letter chart.

Wavefront: a measure of the total focusing errors (aberrations) including mixed astigmatism,and complex focusing errors (higher-order aberrations). Light is projected into your eye andfocused on the retina. Part of this light is reflected back out of your eye to form the wavefront.

Page 26 of 29 7260-0106 Rev. A


K. Patient Assistance Information

To be completed by you or your Primary Eye Care Professional as a reference.

Primary Eye Care Professional

Name:

Address:

Phone:

CustomCornea® LASIK Doctor

Name:

Address:

Phone:

Treatment Location

Name:

Address:

Phone:

Laser Manufacturer

Alcon, Inc.2501 Discovery Drive, Suite 500Orlando, FL 32826Tel: (877) 523-2784 Fax: (407) 384-1677

7260-0106 Rev. A Page 27 of 29

1%b


L. Index

A DAberration 5, See also Focusing Error Diabetes - 13

Definition ·24 Diopter- 8Adverse Events ·17 Definition ·25Allergies 13 Driving' 9Astigmatism - 6, See also Mixed Astigmatism After Surgery - 19

Definition ·24 Dry Eye- 13, 14, 21, 22Autoimmune Disease 12,22,23 Dryness 15, 18

Definition -24Automated Lamellar Keratoplasty (ALK) ·5

Definition · 24 E

Excimer Laser -5, 6B Definition ·25

Eye Tracking 7, 20Burning* 18 Eyeglass Prescription · 5

C FCataract ·12, 20 Farsightedness -6

Definition 24 Definition -25Collagen Vascular Disease. 12.23 Feeling of something in the eye 14, 17, 20

Definition ' 24 Focusing Error- 5, 6. See also AberrationComplications 17 Definition -25Contact Lenses

Bandage 20, 24Discontinue wear before surgery ' 19 G

Contraindications. 12Definition -24 Glare- 14. 15, 18

Contrast Sensitivity- 16 Glaucoma. 13.20Definition -24 Definition · 25

Conventional LASIK -5 Gritty Feeling 18Definition. 24

Cornea -5, 6Definition -24 HFlap 5, 12, 17, 20, 24Infection- 12, 17 Halos - 14, 18Scratch -17 Definition -25Swelling. 14, 17, 25 Headache - 18

CustomCornea® LASIK - Herpes Simplex - 13Are You A Good Candidate - 19 Definition 25Ilerpes Zostcr-' 13Clinical Studies 8, 9, 10, 15. 16. 17 Definitin 15Definition -25I low Does It Correct Mixed Astigmatism -6Questions To Ask Your Doctor. 21Self-Test 22Summary of ImportantInfoinaation -23 Inimunodeficiency Disease · 12What Are The Benefits -8 Definition -25What Are The Risks · 12 Inflammation 17What To Expect During Surgery- 19 Definition 25

Irregular flap · 12

KKeratoconus · 12

Definition · 25

Page 28 of 29 7260-0106 Rev A


L PLADAR6000 System 5,7 Pain · 14, 18, 20

Tracking Eye Movements ·7, 20, 22 Precautions' 13

LADARTracker® System 7, 20 Pregnancy 12, 22, 23

LADARVision ®4000 SystemClinical Studies ·8, 9, 10, 15, 16, 17

Laser Assisted In-Situ Keratomileusis (LASIK) 5 5Definition 25 Radial Keratotomy (RK) ·5

Lens ·6 Definition ·26Definition 25 Reading Glasses · 12, 23

Light Sensitivity 14, 15, 18,20 Redness- 18Retina -6, 17

Definition ·26MMedication

Amiodarone Hydrochloride· 12Antibiotic. 20, 24 Tearing 18Anti-inflanmmatory ·14, 20, 24Isotretinoin 12Steroid ·20, 26 VSumatripin Succinate ·14

Microkeratome · 5, 20 VisionDefinition 26 Blurring 14, 18

Mixed Astigmatism · 5, 6 Double 17, 18Definition 26 Fluctuation - 15, 18

Vision with Glasses -9, 12, 15, 16, 17Vision without Glasses ·9

/N Visual Acuity 9. 15, 16Definition. 26

Nearsightedness 6 Low Contrast 16, 26Definition -26 Mcasurement -8

Night Driving Difficulty 14, 15, 18

W0

Warnings 13Ocular Hypertension 17. 20 Wavefront 5

Definition ·26 Definition -26

7260-0106 Rev. A Page 29 of 29

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